ZYG11A functions as a substrate recruitment subunit in the CRL2 (Cullin-RING ligase 2) ubiquitin ligase complex, playing critical roles in cell cycle regulation and protein quality control 12. The protein participates in targeting cyclin B1 for degradation, working redundantly with the anaphase-promoting complex (APC/C) to facilitate proper mitotic progression and mitotic slippage when APC/C is inactivated 1. ZYG11A also contributes to the glycine-specific N-degron pathway through its related family members ZYG11B and ZER1, which recognize N-terminal glycine degrons for proteasomal degradation 34. The protein shows complex disease associations, functioning as a tumor suppressor in epithelial ovarian cancer where reduced expression correlates with high-grade tumors 5, while acting as an oncogene in non-small cell lung cancer by promoting cell proliferation through CCNE1 expression regulation 6. A missense mutation in ZYG11A (L475P) causes autosomal dominant diabetes by inducing cell cycle arrest in pancreatic beta-cells, impairing their growth and glucose homeostasis function 2. These findings establish ZYG11A as a multifunctional cell cycle regulator with tissue-specific roles in cancer and metabolic disease.