FRMD6 Antibody

What is FRMD6 and why is it important in scientific research?

FRMD6 is a member of the Ezrin/Radixin/Moesin (ERM) family protein and a human homologue of Drosophila expanded (ex). It has emerged as a significant research target due to its involvement in multiple cellular processes and disease pathways. FRMD6 functions as a potential Alzheimer's disease (AD) risk gene as identified through genome-wide association and neuroimaging studies . Additionally, it plays crucial roles in mitochondrial function, with research demonstrating that FRMD6 knockdown leads to mitochondrial dysfunction and fragmentation .

In cancer research, particularly glioblastoma (GBM), FRMD6 appears to function as a tumor suppressor. Studies have shown it is downregulated in human GBM cells and tissues, and increased FRMD6 expression inhibits GBM cell proliferation and invasion both in vitro and in vivo . This dual relevance to both neurodegenerative conditions and cancer makes FRMD6 antibodies valuable research tools for understanding diverse disease mechanisms.

What cellular localization does FRMD6 typically show in immunostaining?

Immunocytochemistry analysis reveals that FRMD6 displays both cytoplasmic and nuclear localization in cells. This was specifically observed in GBM cells expressing v5-tagged FRMD6 protein . The dual localization pattern suggests FRMD6 may have distinct functions in different cellular compartments.

For researchers performing immunostaining with FRMD6 antibodies, it's important to note:

• Both nuclear and cytoplasmic signals should be expected and analyzed

• When studying mitochondrial functions of FRMD6, co-staining with mitochondrial markers is recommended to assess potential mitochondrial association

• Appropriate counterstaining with nuclear dyes helps confirm nuclear localization

• Validation with epitope-tagged FRMD6 (such as v5-tagged constructs used in the literature) can serve as positive controls for staining specificity

This subcellular distribution information proves crucial for interpreting experimental results and understanding FRMD6's potential roles in different cellular compartments and signaling pathways.

What are the key research applications for FRMD6 antibodies?

FRMD6 antibodies serve multiple critical research applications across various experimental platforms:

• Protein expression analysis:

  • Western blotting for detecting and quantifying FRMD6 in different cell types, tissues, and experimental conditions

  • Confirmation of successful FRMD6 knockdown or overexpression in experimental models

  • Assessment of FRMD6 expression changes in response to treatments (e.g., Aβ exposure)

• Cellular localization studies:

  • Immunocytochemistry and immunofluorescence to determine subcellular distribution

  • Co-localization studies with mitochondrial markers to investigate FRMD6's role in mitochondrial function

• Disease-focused investigations:

  • Examining FRMD6 expression in Alzheimer's disease models, particularly in relation to Aβ-induced mitochondrial dysfunction

  • Investigating FRMD6 downregulation in glioblastoma and its relationship to tumor growth

  • Studying FRMD6's interactions with receptor tyrosine kinases (RTKs) like c-Met and PDGFR

• Therapeutic development:

  • Screening for compounds that enhance FRMD6 expression as potential treatments for Alzheimer's disease

  • Evaluating FRMD6 as a potential biomarker or therapeutic target in glioblastoma

  • Validating the effects of FRMD6 overexpression in rescuing disease phenotypes

These applications make FRMD6 antibodies essential tools in both basic science and translational research investigating neurodegenerative diseases and cancer biology.

How does FRMD6 relate to the Hippo signaling pathway?

FRMD6 is the human homologue of Drosophila expanded (ex), which functions upstream of the Hippo signaling pathway. The relationship between FRMD6 and the Hippo pathway appears complex and somewhat controversial based on current research:

Interestingly, research indicates that unlike increased expression of merlin (the human homolog of Drosophila merlin), which enhances stress-induced activation of the Hippo pathway, increased FRMD6 expression displays little effect on the pathway in some experimental contexts . This suggests potential divergence between the functions of Drosophila expanded and human FRMD6, or context-dependent regulation.

For researchers investigating FRMD6-Hippo interactions:

• Both FRMD6 expression and components of the Hippo pathway should be examined simultaneously

• The context-specific effects of FRMD6 must be considered when designing experiments

• Multiple cell types and experimental conditions may be necessary to fully characterize this relationship

This complex relationship requires careful experimental design when using FRMD6 antibodies to study Hippo pathway connections.

What cell types or tissues express significant levels of FRMD6?

Based on available research data, FRMD6 expression has been documented in several cell types:

• Normal human astrocytes express detectable levels of endogenous FRMD6, making them useful positive controls for antibody validation

• Neuronal cells show significant FRMD6 expression:

  • Mouse hippocampal HT-22 cells express FRMD6 and have been used for studying its role in mitochondrial function

  • Primary mouse neurons express FRMD6 and demonstrate mitochondrial dysfunction when FRMD6 is knocked down

• Glioblastoma (GBM) cell lines show variable FRMD6 expression:

  • U251 cells express detectable levels of endogenous FRMD6

  • U87MG cells express little endogenous FRMD6

  • Other GBM cell lines show varying expression levels, with FRMD6 generally downregulated compared to normal astrocytes

This expression pattern information is valuable for researchers selecting appropriate cell models and controls when working with FRMD6 antibodies. The differential expression between normal cells and cancer cells, particularly in the context of glioblastoma, also suggests potential diagnostic or prognostic applications for FRMD6 detection.

How can FRMD6 antibodies be used to study mitochondrial dysfunction in neurodegenerative diseases?

FRMD6 antibodies provide valuable tools for investigating the connection between FRMD6 and mitochondrial dysfunction in neurodegenerative diseases, particularly Alzheimer's disease (AD). Research has established that FRMD6 plays a critical role in maintaining mitochondrial function and that its downregulation by Aβ contributes to mitochondrial dysfunction in AD models .

Several experimental approaches utilizing FRMD6 antibodies can elucidate these mechanisms:

• Monitoring FRMD6 expression changes in response to Aβ:

  • Western blotting with FRMD6 antibodies can quantify protein levels in neuronal cells before and after Aβ treatment

  • Time-course experiments can track how quickly Aβ induces FRMD6 downregulation

• Correlating FRMD6 levels with mitochondrial parameters:

  • Immunofluorescence co-staining using FRMD6 antibodies and mitochondrial markers can examine relationships between FRMD6 expression and mitochondrial morphology

  • Western blotting for FRMD6 alongside markers of mitochondrial dynamics (e.g., OPA1) can assess connections between FRMD6 and mitochondrial fusion/fission processes

Research findings demonstrate that FRMD6 knockdown neurons display:

• Decreased mitochondrial membrane potential

• Reduced complex IV activity

• Decreased ATP production

• Diminished MTT reduction capacity

• Abnormal mitochondrial morphology including mitochondrial swelling

• Increased expression of short OPA1 without changes in total OPA1 levels

Importantly, overexpression of FRMD6 attenuates Aβ-induced perturbations in mitochondrial function, including enhanced production of reactive oxygen species and decreases in metabolic activity . These findings suggest that FRMD6 antibodies are essential for tracking expression in neurodegeneration models and validating therapeutic approaches aimed at enhancing FRMD6 expression.

What are the recommended protocols for detecting FRMD6 expression changes in Alzheimer's disease models?

Based on established research methodologies, several protocols can effectively detect FRMD6 expression changes in Alzheimer's disease (AD) models:

• Western blotting protocol for FRMD6 detection:

  • Treat cells (HT-22 cells or primary neurons) with Aβ at appropriate concentrations

  • Perform cell lysis and protein extraction using buffers that preserve protein integrity

  • Separate proteins via SDS-PAGE and transfer to appropriate membranes

  • Probe with validated FRMD6-specific antibodies (primary) followed by appropriate secondary antibodies

  • Quantify protein levels relative to established loading controls

  • This approach successfully detected Aβ-induced downregulation of FRMD6 protein expression in published studies

• Immunofluorescence protocol for localization studies:

  • Fix and permeabilize neuronal cultures using standard procedures

  • Block with appropriate serum and incubate with FRMD6 primary antibodies

  • Apply fluorescently-tagged secondary antibodies

  • For mitochondrial studies, co-stain with mitochondrial markers (e.g., TOMM20, MitoTracker)

  • Analyze FRMD6 signal intensity and localization patterns

  • This method allows correlation between FRMD6 levels and mitochondrial morphology changes

• Expression manipulation validation:

  • For overexpression: Confirm successful expression using FRMD6 antibodies via immunoblot and immunofluorescence

  • For knockdown: Validate reduced expression using the same methods

  • These validation steps are crucial for interpreting subsequent functional analyses

• Functional assays that correlate with FRMD6 expression:

  • Mitochondrial membrane potential measurement using TMRM staining

  • Complex IV activity assays

  • ATP production quantification

  • MTT reduction capacity

  • Detailed morphological analysis of mitochondria

These protocols have successfully demonstrated that Aβ induces FRMD6 downregulation and that FRMD6 overexpression can rescue Aβ-induced abnormalities in mitochondrial function, morphology, and energetics in AD models.

How does FRMD6 knockdown vs. overexpression affect receptor tyrosine kinase activities, and how can antibodies help assess this?

Research has uncovered a novel mechanism by which FRMD6 influences cellular function, particularly in glioblastoma (GBM), through regulation of receptor tyrosine kinase (RTK) activities. FRMD6 antibodies play a crucial role in investigating this relationship.

The effects of FRMD6 manipulation on RTK activities show distinct patterns:

• FRMD6 overexpression:

  • Reduces phosphorylation/activation of c-Met and PDGFRα/β in GBM cells

  • Inhibits activity of RYK RTK

  • Decreases activation of downstream ERK and AKT kinases

  • Results in reduced GBM cell proliferation and invasion

• FRMD6 knockdown:

  • Enhances GBM cell proliferation and invasion in vitro

  • Promotes GBM growth and progression in vivo

  • Likely increases RTK activity, though not explicitly quantified in available research

Methodological approaches using antibodies to assess FRMD6-RTK relationships include:

• Proteome Profiler Human Phospho-RTK Array analysis:

  • This technique successfully identified c-Met, PDGFR, and RYK as RTKs inhibited by FRMD6 overexpression

  • Provides comprehensive screening of multiple RTKs simultaneously

• Western blotting with phospho-specific antibodies:

  • For targeted validation of specific RTK activity changes

  • Requires phospho-specific antibodies against RTKs of interest (c-Met, PDGFR)

  • Should be paired with FRMD6 antibodies to confirm expression changes

• Functional rescue experiments:

  • Expression of constitutively active RTKs (e.g., TPR-Met fusion protein) in cells with FRMD6 overexpression

  • Confirmation of expression using specific antibodies

  • Assessment of whether RTK activation overcomes FRMD6-mediated effects

Research has demonstrated that expression of constitutively active c-Met (TPR-Met fusion protein) largely reverses the anti-GBM effect of FRMD6 in vivo, suggesting that FRMD6 exerts its anti-GBM effect at least partially through inhibiting c-Met RTK activity . This mechanistic insight provides potential therapeutic targets for GBM treatment.

What are the optimal validation methods for confirming FRMD6 antibody specificity in research applications?

Ensuring FRMD6 antibody specificity is critical for obtaining reliable research results. Based on established research practices, several validation methods are recommended:

• Expression modulation controls:

  • FRMD6 knockdown: Using shRNA-mediated knockdown of FRMD6 provides an excellent negative control for antibody validation

  • FRMD6 overexpression: Retroviral or adeno-associated viral vectors expressing FRMD6 offer positive controls

  • Western blotting should show corresponding decreases or increases in band intensity

  • These approaches confirm that the antibody detects the intended target

• Epitope tag validation:

  • Using v5-epitope tagged FRMD6 (FRMD6v5) as described in published research

  • Parallel detection with anti-tag antibodies (e.g., anti-v5) and anti-FRMD6 antibodies

  • Co-localization of signals confirms antibody specificity

  • Particularly valuable for immunofluorescence validation

• Cell line panel analysis:

  • Utilizing cell lines with known FRMD6 expression profiles (e.g., normal human astrocytes, U87MG, U251)

  • Western blotting should show corresponding signal intensities across these lines

  • This approach validates antibody sensitivity and specificity across a range of expression levels

• Multiple antibody concordance:

  • Using different antibodies targeting distinct epitopes of FRMD6

  • Comparing detection patterns across applications

  • Concordant results increase confidence in specificity

For optimal results, researchers should:

• Include appropriate positive and negative controls in each experiment

• Validate antibodies for each specific application (Western blot, immunofluorescence, etc.)

• Consider potential cross-reactivity with other FERM domain-containing proteins

• Document validation results thoroughly to support research findings

These validation approaches ensure that experimental results accurately reflect FRMD6 biology rather than antibody artifacts.

How can researchers effectively use FRMD6 antibodies to investigate its role in cancer progression?

FRMD6 antibodies serve as valuable tools for investigating this protein's role in cancer progression, particularly in glioblastoma (GBM) where FRMD6 appears to function as a tumor suppressor. Several effective experimental approaches include:

• Expression analysis in patient samples and cell lines:

  • Immunohistochemistry on patient tumor samples to assess FRMD6 expression patterns

  • Western blotting to compare expression levels between normal and cancer cells

  • Research has established that FRMD6 is downregulated in human GBM cells and tissues compared to normal astrocytes

• Functional validation through expression manipulation:

  • FRMD6 knockdown experiments with shRNA followed by proliferation and invasion assays

  • FRMD6 overexpression studies using viral vectors

  • Both approaches require antibody validation of expression changes

• In vivo tumor models with FRMD6 modulation:

  • Subcutaneous xenograft models to assess tumor growth

  • Intracranial models to evaluate cancer progression in the brain microenvironment

  • Immunohistochemistry on tumor sections to confirm FRMD6 expression status

• Mechanistic studies linking FRMD6 to cancer pathways:

  • Analysis of receptor tyrosine kinase (RTK) activity in relation to FRMD6 expression

  • Investigation of downstream signaling pathways (ERK, AKT)

  • Research has demonstrated that FRMD6 inhibits activation of RTKs including c-Met and PDGFR

• Rescue experiments to confirm causality:

  • Expression of constitutively active downstream effectors (e.g., TPR-Met) in FRMD6-overexpressing cells

  • Assessment of whether this rescues the anti-cancer effects of FRMD6

Published research has established that:

• FRMD6 knockdown significantly enhances GBM cell proliferation and invasion in vitro

• FRMD6 knockdown promotes subcutaneous GBM growth and intracranial GBM progression in vivo

• FRMD6 overexpression inhibits GBM cell proliferation and invasion

• These effects are mediated at least partially through inhibition of RTK activity

These findings suggest FRMD6 antibodies are essential tools for cancer research, particularly in studying tumor suppressor mechanisms in glioblastoma.

What protocols yield optimal results for Western blotting with FRMD6 antibodies?

Successful Western blotting with FRMD6 antibodies requires attention to several key technical details:

• Sample preparation considerations:

  • Complete cell lysis is essential; RIPA buffer has been successfully used in published FRMD6 research

  • Include protease inhibitors to prevent degradation

  • For phosphorylation studies (when examining related RTK signaling), phosphatase inhibitors must be added

  • Protein quantification and equal loading are critical for comparative analyses

• Gel electrophoresis parameters:

  • Standard SDS-PAGE conditions are appropriate

  • 8-10% gels typically provide good resolution for FRMD6 detection

  • Include molecular weight markers to confirm the expected size of FRMD6

• Transfer and blocking optimization:

  • Standard transfer protocols to PVDF or nitrocellulose membranes are effective

  • Blocking with 5% non-fat dry milk or BSA in TBST reduces background

  • Optimization of blocking time may be necessary depending on the specific antibody

• Antibody incubation conditions:

  • Primary antibody dilutions must be optimized; published studies have used commercially available FRMD6 antibodies

  • Overnight incubation at 4°C typically provides optimal results

  • Thorough washing steps are essential for reducing background

• Detection systems:

  • Both chemiluminescence and fluorescence-based detection systems have been used successfully

  • For quantitative analysis, fluorescence-based systems provide better linearity

• Controls and validation:

  • Include positive controls (cells known to express FRMD6, such as normal astrocytes)

  • Negative controls should include FRMD6 knockdown samples

  • Loading controls are essential for normalization

• Troubleshooting recommendations:

  • For weak signals: Increase antibody concentration, extend incubation time, or use signal enhancement systems

  • For high background: Increase washing stringency, optimize blocking, or decrease antibody concentration

  • For multiple bands: Verify specificity with knockdown controls, consider using different antibody clones

These protocols have successfully detected FRMD6 in various experimental contexts, including confirmation of knockdown efficiency, validation of overexpression, and assessment of expression changes in response to treatments like Aβ exposure .

How can researchers optimize FRMD6 antibody-based immunofluorescence for colocalization studies?

Optimization of immunofluorescence protocols for FRMD6 colocalization studies requires attention to several critical parameters:

• Fixation and permeabilization considerations:

  • Paraformaldehyde fixation (typically 4%) preserves protein localization

  • Permeabilization with 0.1-0.2% Triton X-100 allows antibody access to intracellular FRMD6

  • For mitochondrial colocalization studies, gentler permeabilization may better preserve mitochondrial morphology

• Antibody selection and validation:

  • Confirm FRMD6 antibody specificity using controls (knockdown, overexpression)

  • For colocalization with mitochondria, select compatible mitochondrial markers (e.g., TOMM20, MitoTracker)

  • For colocalization with RTKs (c-Met, PDGFR), select antibodies raised in different species to avoid cross-reactivity

• Staining protocol optimization:

  • Sequential staining may be preferable to simultaneous incubation

  • Thorough washing between steps reduces background and cross-reactivity

  • Extended primary antibody incubation (overnight at 4°C) often improves signal quality

• Imaging parameters for accurate colocalization assessment:

  • Confocal microscopy with appropriate channel separation prevents bleed-through

  • Z-stack acquisition enables three-dimensional colocalization analysis

  • Consistent exposure settings across experimental conditions enable quantitative comparisons

• Quantitative colocalization analysis methods:

  • Pearson's correlation coefficient or Mander's overlap coefficient for quantifying colocalization

  • Analysis should be performed on multiple cells across independent experiments

  • Software tools (ImageJ with colocalization plugins, CellProfiler) facilitate quantitative analysis

• Controls for colocalization studies:

  • Single-stained samples to set thresholds and check for bleed-through

  • Positive controls using known interacting proteins

  • Negative controls using proteins known not to colocalize

Research has successfully used these approaches to:

• Confirm the cytoplasmic and nuclear localization of FRMD6

• Examine relationships between FRMD6 expression and mitochondrial morphology

• Investigate FRMD6's role in protecting against Aβ-induced mitochondrial fragmentation

These methodological considerations ensure reliable and reproducible results when investigating FRMD6's interactions with cellular structures and other proteins.

What quantitative methods best measure FRMD6 expression changes across experimental conditions?

Accurate quantification of FRMD6 expression changes is essential for understanding its role in disease processes and cellular functions. Several quantitative approaches have proven effective:

• Western blot densitometry analysis:

  • Capture images using linear detection systems (fluorescence-based Western blotting preferred)

  • Normalize FRMD6 band intensity to appropriate loading controls

  • Use software like ImageJ, Image Lab, or specialized Western blot analysis programs

  • Include standard curves when possible for absolute quantification

  • This approach successfully quantified FRMD6 expression changes in published studies

• Immunofluorescence intensity quantification:

  • Maintain consistent imaging parameters across all experimental conditions

  • Measure mean fluorescence intensity within defined cellular regions

  • Analyze multiple cells per condition (typically >30) across independent experiments

  • This method allows assessment of both expression levels and subcellular distribution changes

• qRT-PCR for mRNA expression analysis:

  • While not explicitly mentioned in the search results, this complementary approach verifies transcriptional changes

  • Requires careful primer design specific to FRMD6

  • Normalization to multiple reference genes enhances reliability

• Flow cytometry for single-cell quantification:

  • Enables analysis of large cell populations

  • Provides distribution data rather than just mean values

  • Requires optimization of cell permeabilization for intracellular FRMD6 detection

• Statistical analysis considerations:

  • Apply appropriate statistical tests based on data distribution

  • Report effect sizes alongside statistical significance

  • Account for biological and technical variability

  • Power analysis ensures adequate sample sizes

• Experimental design for robust quantification:

  • Include relevant controls (positive, negative, knockdown, overexpression)

  • Perform time-course experiments to capture dynamic changes

  • Use multiple complementary quantification methods when possible

These approaches have successfully quantified FRMD6 expression changes in various experimental contexts, including:

• Downregulation in response to Aβ treatment

• Decreased expression in GBM compared to normal astrocytes

• Confirmation of knockdown efficiency using shRNA

• Validation of overexpression in cells transduced with FRMD6 expression constructs

Selecting the appropriate quantification method depends on the specific research question, available materials, and required sensitivity.

How can FRMD6 antibodies be effectively used in high-throughput screening applications?

While the search results don't specifically detail high-throughput screening (HTS) with FRMD6 antibodies, the following approaches can be developed based on established principles and the FRMD6 research context:

• Microplate-based immunoassay development:

  • Adapt ELISA formats for FRMD6 detection in cell lysates

  • Optimize antibody pairs (capture and detection) for specificity and sensitivity

  • Validate with known FRMD6 expression modulators (e.g., Aβ treatment reduces expression)

• Automated Western blot systems:

  • Utilize capillary-based automated Western platforms

  • Standardize sample preparation and loading

  • Develop protocols for consistent FRMD6 detection across multiple samples

• High-content imaging approaches:

  • Immunofluorescence in microplate format with automated image acquisition

  • Develop algorithms for quantifying FRMD6 expression and localization

  • Particularly valuable for screening compounds that affect FRMD6 in the context of:

    • Mitochondrial morphology and function in neurodegenerative disease models

    • Cell proliferation and invasion in glioblastoma models

• Flow cytometry screening:

  • Develop protocols for intracellular FRMD6 staining compatible with flow cytometry

  • Enable rapid assessment of expression changes across large cell populations

  • Allows multiparameter analysis with other cellular markers

• Compound library screening applications:

  • Screen for molecules that upregulate FRMD6 as potential therapeutics for Alzheimer's disease

  • Identify compounds that restore FRMD6 expression in glioblastoma cells

  • Test for agents that modulate FRMD6's effects on RTK signaling

• Technical considerations for HTS implementation:

  • Ensure antibody lot consistency throughout screening campaigns

  • Include appropriate positive and negative controls on each plate

  • Develop robust statistical methods for hit identification

  • Establish secondary validation assays for confirming primary hits

• Functional readouts that can accompany FRMD6 detection:

  • Mitochondrial function assays (membrane potential, ROS production)

  • Cell proliferation and invasion measurements

  • RTK activity assessment

These approaches would enable screening of compound libraries, genetic modifiers, or environmental factors that influence FRMD6 expression or function, potentially identifying therapeutic strategies for conditions where FRMD6 dysregulation plays a role.

What are the key considerations when developing therapeutic strategies targeting FRMD6?

The search results suggest potential therapeutic applications targeting FRMD6 in both Alzheimer's disease and glioblastoma. Key considerations for developing such strategies include:

• Therapeutic approaches for Alzheimer's disease:

  • Enhancing FRMD6 expression appears beneficial, as research demonstrates that:

    • FRMD6 overexpression attenuates Aβ-induced toxicity

    • FRMD6 overexpression rescues Aβ-induced abnormalities in mitochondrial morphology and function

    • Increasing FRMD6 protects against Aβ-induced imbalance in mitochondrial dynamics

• Therapeutic approaches for glioblastoma:

  • Restoring FRMD6 expression might inhibit tumor growth, as evidence shows:

    • FRMD6 is downregulated in human GBM cells and tissues

    • Increased FRMD6 expression inhibits GBM cell proliferation and invasion

    • FRMD6 knockdown promotes GBM growth and progression in vivo

• Mechanistic considerations for drug development:

  • For Alzheimer's disease: Target mitochondrial dysfunction pathways

  • For glioblastoma: Consider FRMD6's role in inhibiting RTK activities (c-Met, PDGFR)

  • Understanding these distinct mechanisms is crucial for developing disease-specific approaches

• Therapeutic modality options:

  • Gene therapy approaches to restore or enhance FRMD6 expression

  • Small molecules that upregulate endogenous FRMD6

  • Peptide mimetics that replicate FRMD6's interactions with key targets

  • Combination therapies targeting FRMD6 alongside established treatment approaches

• Biomarker development for patient stratification:

  • FRMD6 antibodies would be essential for developing companion diagnostics

  • Identifying patients most likely to benefit from FRMD6-targeted therapies

  • Monitoring treatment response through FRMD6 expression or activity assessment

• Challenges in therapeutic development:

  • Tissue-specific delivery of FRMD6-modulating agents

  • Potential off-target effects given FRMD6's multiple functions

  • Overcoming the blood-brain barrier for neurological applications

  • Determining optimal timing of intervention in disease progression

The research suggests that for Alzheimer's disease, approaches that enhance Willin/FRMD6 expression hold potential as therapeutic strategies for protecting against Aβ-induced mitochondrial and neuronal dysfunction . For glioblastoma, restoring FRMD6 expression or mimicking its inhibitory effects on RTK activity could represent promising treatment avenues .