EPN1 (epsin 1) is a ubiquitin-binding endocytic clathrin adaptor that regulates receptor-mediated endocytosis by binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-enriched membranes and facilitating clathrin-coated vesicle formation. The ENTH domain of EPN1 possesses membrane vesiculation activity and remodels membrane curvature to promote endocytic invaginations 1. EPN1 functions as a key component of clathrin-mediated endocytosis (CME) protein interaction networks, where it is recruited during CME site stabilization and growth alongside adaptor proteins like AP2 2. Clinically, EPN1 has relevance in cancer progression. In bladder cancer, EPN1-mediated endocytosis of SNAT2 is suppressed by ubiquitination crosstalk, leading to increased SNAT2 membrane localization, enhanced glutamine uptake, and promotion of lymphangiogenesis and lymph node metastasis 3. Conversely, loss of endothelial EPN1 in tumors impairs VEGFR2 endocytosis and degradation, resulting in excessive VEGF signaling that compromises tumor vascular function and retards tumor growth 4. EPN1 is also identified as a hub gene in pediatric medulloblastoma pathogenesis 5 and correlates with molecular subtypes in meningioma 6. Additionally, EPN1 represents a novel protein showing significant changes during high-intensity interval training responses in human skeletal muscle 7.