COP1 is an E3 ubiquitin ligase that mediates proteasomal degradation of multiple substrate proteins, functioning as a RING domain subunit within larger E3 ubiquitin ligase complexes 1. Primary substrates include p53, c-Jun, c/EBPβ, c/EBPδ, FOXO1, and 14-3-3σ, whose degradation suppresses tumor suppression and apoptosis 234. In cancer immunotherapy, COP1 deletion in tumor cells stabilizes c/EBPδ, reducing macrophage chemoattractant secretion and enhancing anti-tumor immunity with improved checkpoint blockade response in triple-negative breast cancer 4. In neuroinflammation, COP1 suppresses pathogenic microglial activation by degrading c/EBPβ; COP1 deficiency accelerates tau-mediated neurodegeneration through complement-dependent mechanisms 3. COP1 exhibits context-dependent roles: in glucose-driven tumorigenesis, COP1-mediated p53 degradation promotes glycolysis and cancer cell proliferation, while disrupting COP1-p53 interaction reverses hyperglycemia-induced tumorigenesis 2. In hepatocellular carcinoma, TRIB3-recruited COP1 degrades FOXO1, promoting MET-driven tumor development 5. These dual tumor-promoting and immune-suppressive functions identify COP1 as a potential therapeutic target for cancer immunotherapy and metabolic disease management.