FRMD4A (FERM domain containing 4A) is a scaffolding protein that plays critical roles in epithelial cell polarity regulation and protein secretion. The protein regulates tau (MAPT) secretion through cytohesin-Arf6 signaling pathways, where FRMD4A overexpression increases tau secretion while depletion reduces it 1. FRMD4A functions in epithelial polarization by connecting ARF6 activation with cell polarity complexes, working redundantly with FRMD4B 1. In disease contexts, FRMD4A exhibits oncogenic properties in squamous cell carcinomas, where upregulation correlates with tumor growth, metastasis, and poor prognosis 2. FRMD4A silencing in cancer cells reduces proliferation, increases apoptosis, and causes nuclear YAP accumulation, suggesting involvement in Hippo signaling 2. The gene also serves as a tumor marker in sarcomatoid clear cell renal carcinoma 3. Clinically, FRMD4A mutations cause neurodevelopmental disorders including corpus callosum agenesis, cerebellar ataxia, and intellectual disability 4. Additionally, FRMD4A variants are associated with congenital microcephaly 5 and smoking behavior traits 6. The protein's dual roles in normal cellular function and disease pathogenesis make it both a developmental regulator and potential therapeutic target.