COPS6 (COP9 signalosome subunit 6) is a core component of the COP9 signalosome complex, functioning as an essential regulator of the ubiquitin conjugation pathway through deneddylation of cullin E3 ligase subunits 1. The complex mediates phosphorylation of critical regulatory proteins including p53, c-jun, and IκBα, modulating their proteasomal degradation [UniProt]. COPS6 has emerged as a significant oncogene across multiple cancer types. High COPS6 expression correlates with poor prognosis in colorectal cancer, hepatocellular carcinoma, breast cancer, and other malignancies 2. Mechanistically, COPS6 promotes cancer progression through multiple pathways: in colorectal cancer, ALDOA-mediated COPS6 upregulation activates MAPK signaling and epithelial-mesenchymal transition 3; in breast cancer, COPS6 overexpression stimulates p-AKT and suppresses CD8+ T cell infiltration via IL-6 production, facilitating immune evasion 4. In colorectal cancer, the ZNF460/METTL5/COPS6 axis regulates m6A-mediated mRNA stabilization to promote immune escape 5. Beyond cancer, desmosomal COPS6 restricts proteome degradation; loss of junctional COPS6 triggers arrhythmogenic right ventricular dysplasia/cardiomyopathy 6. COPS6 represents a promising biomarker for cancer prognosis and therapeutic targeting.