UBE2S is a ubiquitin-conjugating enzyme that catalyzes the formation of K11-linked polyubiquitin chains and plays critical roles in cell cycle regulation and cancer progression. As an essential component of the anaphase-promoting complex/cyclosome (APC/C), UBE2S specifically elongates K11-linked polyubiquitin chains on APC/C substrates, promoting their proteasomal degradation and facilitating mitotic exit 1. The enzyme functions by accepting ubiquitin from E1 complexes and transferring it to target proteins, with particular specificity for K11 linkages rather than the more common K48 linkages 2. UBE2S demonstrates significant disease relevance in multiple cancer types, where its overexpression correlates with poor prognosis and enhanced tumor progression 34. In hepatocellular carcinoma, UBE2S promotes glycolysis through E3-independent K11-linked polyubiquitination of VHL, leading to HIF-1α stabilization 5. Additionally, UBE2S contributes to cancer cell cycle progression by interacting with TRIM28 to mediate p27 degradation 6, and promotes metastasis through TRIM21-mediated degradation of LPP in bladder cancer 2. Clinically, UBE2S represents a promising therapeutic target, with small molecule inhibitor cephalomannine showing efficacy in multiple cancer models 627.