ANAPC5 is a core subunit of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase essential for mitotic progression and G1 phase control 1. The APC/C complex mediates ubiquitination and degradation of cell cycle regulators, primarily forming Lys-11-linked polyubiquitin chains and branched Lys-11/Lys-48-linked chains on target proteins 12. Beyond canonical cell cycle functions, ANAPC5 demonstrates disease-relevant roles: radiation exposure inhibits APC/C activity, reducing ANAPC5-mediated ubiquitination of GPAA1, which promotes GPI anchoring and CD24 membrane trafficking, enabling tumor immune evasion 3. In neuroblastoma, ANAPC5 upregulation correlates with chemoresistance to cisplatin and oncogene-induced senescence 45. ANAPC5 expression associates with lung squamous cell carcinoma progression and pathological staging 6, and shows positive correlation with cell cycle progression in acute lymphoblastic leukemia 7. Notably, ANAPC5 polymorphisms associate with susceptibility to HIV-associated sensory neuropathy 89, suggesting broader roles beyond cell cycle regulation. ANAPC5 also acts as a genetic modifier of KIF18A-dependent mitotic fidelity, with differential expression influencing sensitivity to mitotic disruption 10.