UBE3C is an E3 ubiquitin ligase that catalyzes Lys-29- and Lys-48-linked polyubiquitin chain assembly, preferentially forming Lys-48 linkages 12. It accepts ubiquitin from E2 enzyme UBE2D1 and transfers it to substrate proteins 3. UBE3C functions in multiple regulatory pathways: it negatively regulates antiviral immunity by mediating IRF3 degradation during the late stage of viral infection, allowing timely resolution of innate responses 4; suppresses autophagy by ubiquitinating and degrading VPS34 5; and regulates protein aggregate turnover in a proteasome-dependent manner independent of autophagy involvement 6. In cancer contexts, UBE3C promotes progression by ubiquitinating and degrading tumor suppressors: p53 in pancreatic cancer 7, PEBP1 in renal carcinoma 8, and AHNAK in osteosarcoma 9. Biallelic loss-of-function variants in UBE3C cause neurodevelopmental disorders with absent speech, movement abnormalities, and behavioral features overlapping Angelman syndrome, establishing UBE3C as a novel disease gene 10.