USP31 (ubiquitin-specific peptidase 31) is a deubiquitinating enzyme that regulates protein stability through ubiquitin hydrolysis 1. The enzyme contains conserved ubiquitin hydrolase domains and is primarily expressed in testis and lung tissue 1. Mechanistically, USP31 functions as a deubiquitinase that stabilizes target proteins by removing ubiquitin modifications. Notably, USP31 specifically binds and deubiquitinates GPX4, a glutathione peroxidase involved in antioxidant defense and ferroptosis regulation 2. USP31 also stabilizes β-catenin in the Wnt signaling pathway 3 and E2F1 transcription factor 4, promoting their respective downstream signaling cascades. In disease contexts, USP31 demonstrates dual roles. In cardiovascular disease, macrophage-expressed USP31 promotes atherosclerosis development through NF-κB pathway activation 5. Conversely, in multiple cancer types including hepatocellular carcinoma, cervical cancer, gastric cancer, lung squamous cell carcinoma, and clear cell renal cell carcinoma, USP31 upregulation correlates with poor prognosis and enhanced tumor progression 26347. USP31 suppression increases cancer cell radiosensitivity by promoting ferroptosis 6. Clinically, USP31 represents a potential biomarker for cancer prognosis and therapeutic targeting, with its inhibition showing promise for enhancing cancer treatment efficacy.