EPB41L5 is a FERM domain protein that functions as a critical regulator of epithelial cell polarity and architectural integrity. Structurally, EPB41L5 oligomerizes through its FERM-adjacent domain, with this multimerization essential for its role in limiting apical membrane growth and maintaining polarized epithelial organization 1. The protein also regulates mechanotransduction in specialized epithelial cells; in podocytes, EPB41L5 loss impairs YAP/TAZ-dependent signaling and ARHGAP29 expression, leading to defective lamellipodia formation and slit diaphragm dysfunction 2. In proximal tubular epithelial cells, EPB41L5 serves as a differentiation marker, with its downregulation associated with dedifferentiation during lipotoxic stress 3. Disease relevance extends to cancer progression: EPB41L5 expression is elevated in gastric cancer patients with poor prognosis and mediates TGFβ-induced metastasis through p120-catenin interaction 4. Similarly, EPB41L5 is required for both mesenchymal and amoeboid invasion modes through the Arf6-AMAP1-EPB41L5-ZEB1 axis 5. Conversely, in glioblastoma, the tumor suppressor ZBTB7A represses EPB41L5 transcription to inhibit progression 6, and circular EPB41L5 functions as a glioma suppressor by regulating the miR-19a/EPB41L5/AKT axis 7. EPB41L5 appears as a candidate disease gene in Mendelian disease studies 8, suggesting broader clinical significance beyond cancer biology.