USP12 is a deubiquitinating enzyme that removes ubiquitin modifications from target proteins to regulate their stability and cellular localization. USP12 functions as part of a ternary complex with cofactors WDR48 (UAF-1) and WDR20, which are required for its catalytic activity 1. The enzyme exhibits diverse substrate specificity, deubiquitinating histones H2A and H2B to regulate gene expression during development 2, stabilizing β1 integrin by preventing ESCRT-mediated lysosomal degradation 3, and deubiquitinating RRM2 to promote DNA synthesis 4. USP12 also stabilizes c-Myc through WDR20-mediated deubiquitination 5 and regulates androgen receptor stability in prostate cancer 1. In cancer contexts, USP12 displays complex roles: it can act as a tumor suppressor when downregulated in KRAS-driven lung cancer, where loss of USP12 promotes immunosuppressive microenvironments through PPM1B-NF-κB signaling 6, yet also functions as an oncogene in other contexts by stabilizing pro-tumorigenic proteins. The enzyme's dysregulation contributes to various diseases including multiple cancers, cardiac hypertrophy, and bone disorders 78, making it a potential therapeutic target with context-dependent functions requiring careful consideration for clinical applications.