EPB41 encodes protein 4.1R, a major structural component of the erythrocyte membrane cytoskeleton that stabilizes spectrin-actin interactions and regulates membrane mechanical properties 1. Beyond its classical role in red blood cells, EPB41 functions as a cytoskeletal adaptor protein with broader cellular roles. It recruits DLG1 to membranes and is required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase, suggesting involvement in cell division regulation. Clinically, EPB41 mutations cause hereditary elliptocytosis (HE), a red blood cell membrane disorder characterized by elliptical erythrocytes and variable anemia severity 2. Recent studies reveal EPB41's tumor suppressor function in non-small cell lung cancer, where it suppresses Wnt/β-catenin signaling through the EPB41/ALDOC/GSK3β/β-catenin axis; reduced EPB41 expression correlates with poor prognosis 3. In dendritic cells, EPB41 knockdown impairs migration and alters immune function, implicating it in autoimmune pathogenesis 4. Additionally, EPB41 shows diagnostic potential as a plasma biomarker for sport-related concussion, with optimal predictive value when combined with alpha-synuclein 5. EPB41 also appears associated with mandibular prognathism susceptibility 67.