EPB41L4B is a FERM-domain cytoskeletal protein that regulates epithelial cell structure and proliferation through multiple mechanisms. It functions as an essential mediator of CRB3-driven proliferation in mammary epithelial cells by modulating endocytic trafficking and amphiregulin secretion 1. EPB41L4B positively regulates cell adhesion and migration in vitro and may contribute to wound healing [UniProt annotation]. The protein is involved in organizing the circumferential actomyosin belt in epithelial cells [UniProt annotation], supporting its role in maintaining epithelial architecture. Clinically, EPB41L4B has emerging relevance in multiple diseases. In ulcerative colitis, elevated EPB41L4B expression characterizes a molecular subgroup with mild disease severity but increased progression risk to colorectal cancer 2. In prostate cancer, EPB41L4B upregulation is associated with ERG overexpression and earlier biochemical recurrence 3. In breast cancer, EPB41L4B functions as a prognostic biomarker; high expression correlates with worse survival outcomes and immunosuppressive microenvironment, while its knockdown inhibits cell viability and migration while promoting apoptosis 4. Additionally, EPB41L4B shows dysregulation at both DNA methylation and transcriptome levels in placentas from pregnancies complicated by maternal anxiety and depression, suggesting potential epigenetic biomarker value 5. EPB41L4B was identified as a respiratory disease biomarker upregulated in RSV-infected bronchial epithelial cells 6.