FBXO5 (F-box protein 5) is a critical regulator of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase during cell cycle progression. During G1 phase, FBXO5 functions as an APC/C substrate, but switches to an APC/C inhibitor during S and G2 phases to promote cell-cycle commitment 1. As an inhibitor, FBXO5 prevents APC/C-mediated degradation of substrates by blocking D-box receptor access and suppressing ubiquitin conjugation activities of E2 enzymes UBE2C and UBE2S 23. This inhibitory function stabilizes cyclins and geminin, coordinating DNA replication with mitosis and preventing genomic instability 45. FBXO5 also promotes migration and osteogenic differentiation of mesenchymal stem cells 6. In cancer contexts, FBXO5 is frequently upregulated and associates with poor prognosis across multiple tumor types 7. FBXO5 expression correlates with immunosuppressive immune microenvironments, elevated Treg cells, and reduced CD8+ T cell infiltration 7. In colon cancer, FBXO5 promotes progression by degrading RNF183, an E3 ligase regulating endoplasmic reticulum stress-induced apoptosis 8. In glioblastoma, FBXO5-mediated degradation of DOK6 mediates temozolomide resistance through proteasome-cytomechanics regulation 9. These findings position FBXO5 as a potential immunotherapeutic and chemotherapeutic target across malignancies.