UBE2D2 is an E2 ubiquitin-conjugating enzyme that accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to target proteins, primarily through Lys-48-linked polyubiquitination 123. It mediates selective degradation of short-lived and abnormal proteins and functions in E6/E6-AP-induced ubiquitination of p53 4. UBE2D2 regulates ubiquitination of multiple substrates including VEGFR2, PEX5, and SQSTM1, and is essential for viral activation of IRF3 56. In cancer contexts, UBE2D2 overexpression correlates with poor prognosis across multiple tumor types and is associated with immune checkpoint marker expression 7. In gastric cancer, UBE2D2 promotes progression by inhibiting ferroptosis through stabilization of CST1, and this pathway represents a therapeutic target 8. In breast cancer, circular RNA derived from UBE2D2 mediates tamoxifen resistance through a miR-200a-3p-dependent mechanism 9. Multi-omics analysis identified UBE2D2 as one of eight circulating proteins causally associated with intervertebral disc degeneration 10. These findings position UBE2D2 as a potential prognostic biomarker and therapeutic target in cancer and degenerative disease, though specific inhibitors remain under investigation.