USP7 (ubiquitin-specific peptidase 7) is a cysteine-type deubiquitinase that regulates protein stability through K48-linked polyubiquitin chain removal 1. Mechanistically, USP7 binds target proteins via its TRAF domain and removes ubiquitin modifications, stabilizing substrates including KRAS 1, KDM5B 2, PD-L1 3, TRIM24 4, and SCD 5. In cancer pathogenesis, USP7 promotes tumorigenesis across multiple mechanisms. USP7 stabilizes oncogenic KRAS, driving non-small cell lung cancer proliferation, with high USP7 expression correlating with poor survival and resistance to KRAS-G12C inhibitors 1. In nasopharyngeal carcinoma, USP7-mediated KDM5B stabilization promotes cisplatin resistance through the ZBTB16/TOP2A axis 2. USP7 also protects PD-L1 from degradation, enabling immune evasion across multiple cancer types 3. Conversely, in gastric cancer, USP7 inhibition induces ferroptotic cell death through SCD degradation 5. Clinically, USP7 represents a promising therapeutic target. USP7 inhibitors suppress cancer cell proliferation, particularly in drug-resistant contexts 1. Blocking USP7 synergizes with PD-L1 checkpoint inhibitors by promoting PD-L1 degradation and enhancing anti-tumor immunity 3. USP7 also regulates metabolic disorders 6 and is associated with Hao-Fountain syndrome, though inhibitors currently lack clinical approval.