COPS5 (COP9 signalosome subunit 5), also known as Jab1, functions as the catalytic subunit of the COP9 signalosome complex, mediating protein deneddylation and deubiquitination activities 12. The protein plays critical roles in regulating protein stability through ubiquitin-proteasome pathways, including stabilization of PD-L1 by inhibiting its ubiquitination and degradation 1, and stabilization of MK2 through deubiquitination 3. COPS5 demonstrates significant oncogenic properties across multiple cancer types, with overexpression frequently observed in hepatocellular carcinoma, colorectal cancer, osteosarcoma, and triple-negative breast cancer 4562. The protein contributes to cancer progression through multiple mechanisms: promoting ferroptosis resistance via MK2-HSPB1 signaling 3, enhancing homologous recombination repair by stabilizing HRR-related mRNAs 2, and activating PI3K/AKT pathways through 14-3-3σ degradation 5. Clinically, COPS5 overexpression correlates with poor prognosis and drug resistance, while its inhibition sensitizes cancer cells to PARP inhibitors and anti-CTLA4 therapy 172. These findings establish COPS5 as both a prognostic biomarker and potential therapeutic target in cancer treatment.