USP37 is a deubiquitinase essential for maintaining genome stability and regulating cell cycle progression. Mechanistically, USP37 catalyzes deubiquitination of specific protein substrates, particularly those modified with Lys-11-linked polyubiquitin chains 1. During S phase entry, USP37 stabilizes cyclin A by antagonizing APC/C-mediated degradation, promoting G1/S transition 1. USP37 protects replication fork integrity by deubiquitinating the CMG helicase complex (CDC45-MCM-GINS) and replication protein A (RPA), preventing premature replisome disassembly 234. Additionally, USP37 sustains DNA damage responses by stabilizing the BLM helicase following ATM-mediated phosphorylation upon DNA double-strand breaks 1. Clinically, USP37 dysfunction associates with enhanced PARPi sensitivity in BRCA1-deficient tumors, identifying it as a potential therapeutic target 5. In osteosarcoma and nasopharyngeal carcinoma, elevated USP37 expression correlates with poor prognosis and promotes metastasis through interactions with PCNA and STAT3-mediated transcriptional regulation 67. Notably, CDK1-mediated phosphorylation at threonine 631 enhances USP37 activity in colorectal cancer progression 8.