ANAPC4 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 regulation 1. The APC/C catalyzes ubiquitination and degradation of cell cycle proteins, predominantly forming Lys-11-linked polyubiquitin chains and branched Lys-11/Lys-48-linked chains on target substrates 12. Recent mechanistic studies reveal that accumulated lactate directly inhibits SENP1, a SUMO protease, causing stabilized SUMOylation of ANAPC4 residues that enhance UBE2C binding and promote timely degradation of cell cycle proteins during mitotic exit 3. This lactate-dependent APC/C remodeling coordinates nutrient availability with cell proliferation but can drive aberrant mitotic progression when persistently elevated. Beyond cell cycle control, ANAPC4 variants associate with multiple disease phenotypes: genetic studies identify ANAPC4 loci linked to Parkinson's disease through shared olfactory function pathways 4, cardiovascular-kidney-metabolic syndrome and sarcopenia comorbidity via epigenetic mechanisms 5, osteoarthritis with metabolic traits 6, and chr4 pain in COVID-19 patients 7. In cancer biology, ANAPC4 downregulation promotes papillary thyroid cancer growth 8, while ANAPC4 mutations associate with trastuzumab resistance in HER2-positive breast cancer 9. These findings establish ANAPC4 as a central node integrating cell cycle control with metabolic and disease-relevant regulatory networks.