CDC20 is a substrate-specific adapter of the anaphase-promoting complex/cyclosome (APC/C) that confers substrate specificity by recognizing destruction box motifs on protein substrates and targeting them for ubiquitin-dependent degradation 1. During mitosis, CDC20 activity is regulated by MAD2L1: metaphase inhibition maintains mitotic checkpoint control, while anaphase activation promotes substrate degradation and cell cycle progression 2. Alternative CDC20 translational isoforms modulate mitotic arrest duration; downstream-initiated truncated isoforms resist checkpoint inhibition and promote mitotic exit even with unresolved errors 3. Beyond cell cycle regulation, CDC20-APC/C mediates specialized cellular functions including autophagy regulation through PBRM1 ubiquitination 4 and ER stress modulation via TPD52 degradation 5. CDC20 is frequently dysregulated in cancer: overexpression promotes hepatocellular carcinoma radioresistance via Bcl-2/Bax pathway modulation 6, and circadian-driven upregulation accelerates pituitary adenoma progression through cell cycle gene transcription 7. Conversely, promoter variants reducing CDC20 expression in melanoma increase xenograft growth 8. In acute kidney injury, CDC20 acts as a negative autophagy regulator; inhibiting CDC20 protects against cisplatin-induced tubular damage 9. These findings position CDC20 as an oncogenic target warranting therapeutic intervention across multiple cancers 10.