UBE2D1 (ubiquitin-conjugating enzyme E2 D1) is an E2 enzyme that accepts ubiquitin from E1 complexes and catalyzes covalent attachment to substrate proteins, primarily mediating Lys-48-linked polyubiquitination 12. The enzyme facilitates selective degradation of short-lived and abnormal proteins, including p53/TP53 in the E6/E6-AP pathway, and regulates VEGFR2 dynamics by controlling receptor trafficking and proteolysis 3. UBE2D1 functions in multiple ubiquitination pathways: it mediates PEX5 ubiquitination, auto-ubiquitination of STUB1 and TRAF6, and viral IRF3 activation 4. Clinically, UBE2D1 dysregulation associates with several cancers. In hepatocellular carcinoma (HCC), UBE2D1 overexpression promotes tumor progression through p53 degradation and genomic copy number gain linked to IL-6 signaling 5. The miR-101/UBE2D1 axis regulates HCC chemotherapy sensitivity, with elevated UBE2D1 conferring chemoresistance to cisplatin and 5-fluorouracil 6. In breast cancer, IGF2BP2-mediated m6A modification increases UBE2D1 mRNA stability, promoting proliferation and migration via Smad2/3 modulation 7. Additionally, UBE2D1 serves as a potential biomarker in systemic juvenile idiopathic arthritis, where elevated expression in monocytes correlates with disease activity through NLR pathway activation 8.