UBE2D2 (ubiquitin conjugating enzyme E2 D2) is an E2 ubiquitin-conjugating enzyme that catalyzes the covalent attachment of ubiquitin to substrate proteins 1. It catalyzes Lys-48-linked polyubiquitination 2, mediating selective degradation of short-lived and abnormal proteins 3. UBE2D2 functions in diverse cellular pathways, including p53 regulation through E6/E6-AP and MDM2 signaling 4, NFKBIA degradation 5, and viral immunity through IRF3 activation 6. In endothelial cells, UBE2D2 regulates VEGFR2 ubiquitination and plasma membrane dynamics to modulate angiogenic signaling 7. UBE2D2 is essential for Parkin-dependent mitophagy of depolarized mitochondria 8. Clinically, UBE2D2 is frequently overexpressed across multiple cancer types and serves as a prognostic biomarker 9. In gastric cancer, UBE2D2 promotes tumor progression by inhibiting ferroptosis through autophagy-dependent stabilization of CST1, suggesting the UBE2D2-CST1-GPx4 pathway as a therapeutic target 10. Notably, circular RNA-UBE2D2 promotes non-small cell lung cancer and breast cancer progression through competing endogenous RNA mechanisms 11 12.