COPS8 (COP9 signalosome subunit 8) is a core component of the COP9 signalosome complex, functioning as a key regulator of protein ubiquitylation and cellular signaling. COPS8 mediates deneddylation of cullin-containing E3 ligase complexes, particularly through CUL4A-RBX1-COPS8 E3 ligase activity required for CENP-A K124 ubiquitylation at centromeres 1, which is essential for centromere-specific histone deposition and chromosome 2 2. The complex also participates in phosphorylation of signaling proteins via association with kinases, regulating NF-κB activation pathways 3. Clinically, COPS8 dysregulation is implicated in multiple cancers. In cutaneous melanoma, COPS8 is upregulated and promotes tumor progression through epithelial-mesenchymal transition (EMT), correlating with poor prognosis 4. In lung adenocarcinoma, COPS8 stabilizes PD-L1 protein through ubiquitin-mediated degradation inhibition downstream of F2RL1 signaling, facilitating tumor immune evasion 5. Additionally, COPS8 upregulation is associated with phlegm-dampness constitution phenotype linked to metabolic disease susceptibility 6. Genetic variants in COPS8 have been examined in familial renal cell carcinoma contexts 7, suggesting potential role in hereditary cancer predisposition.