COPS9 is a structural subunit of the COP9 signalosome (CSN), a conserved multi-protein complex that negatively regulates neddylation of cellular proteins, including the ribosomal protein RPL11 1. As part of the CSN, COPS9 functions to inhibit cullin-RING ubiquitin ligases (CRLs)—the largest family of E3 ubiquitin ligases—through both enzymatic deneddylation and nonenzymatic steric mechanisms 2. This regulation is critical for controlling protein ubiquitination pathways and maintaining cellular proteostasis 2. COPS9 has significant clinical relevance in hepatocellular carcinoma (HCC), where it is substantially upregulated and serves as an independent prognostic biomarker for overall survival 3. High COPS9 expression correlates with shorter survival, increased metastatic capacity, and enhanced immune cell infiltration in HCC tissues 3. Additionally, COPS9 dysregulation has been implicated in HIV-1 pathogenesis, with altered expression observed during acute infection affecting immune cell transcriptional programs 4. In lymphomas, COPS9 (JAB1) interacts with cell-cycle regulators like p27 and cyclins, influencing proliferative control 5. COPS9 knockout studies in HCC cells reduce proliferation and metastasis, confirming its functional importance in cancer biology 3.