REPS2 (RALBP1-associated Eps domain containing 2) is a multifunctional adaptor protein that regulates receptor-mediated endocytosis and cell signaling. Its primary function involves controlling ligand-dependent endocytosis of growth factor receptors, particularly EGF and insulin receptors, through the Ral signaling pathway 1. REPS2 contains Eps15 homology domains and proline-rich regions that facilitate protein-protein interactions essential for receptor internalization 2. By modulating growth factor receptor trafficking, REPS2 suppresses growth factor signaling and cell proliferation 1. Additionally, REPS2 regulates cell adhesion and migration through ASAP1 interaction and may inhibit Wnt signaling via autophagy-mediated β-catenin degradation 3. Loss of REPS2 expression occurs during cancer progression and is associated with enhanced cell proliferation and poor clinical outcomes in prostate and esophageal cancers 14. REPS2 downregulation in lens epithelial cells facilitates fibroblast growth factor-induced migration and posterior capsule opacification through FAK/Cdc42 signaling, contributing to cataract pathogenesis 5. REPS2 demonstrates clinical relevance as a favorable prognostic marker in breast cancer and may protect against neuroinflammation through ERBB pathway regulation 67.