USP5

USP5, also known as ubiquitin-specific protease 5 or isopeptidase T, is a cysteine protease that catalyzes the hydrolysis of ubiquitin chains, primarily disassembling unanchored polyubiquitin and recycling ubiquitin monomers. It regulates protein stability by reversing ubiquitination, thereby influencing diverse cellular processes including cell cycle progression, DNA repair, and stress responses.
USP5 participates in pathways such as the NF-κB signaling cascade, where it modulates IκBα degradation, and the p53 network by stabilizing target proteins. Dysregulation is linked to cancer, with overexpression observed in colorectal and breast cancers, and neurodegenerative disorders like Parkinson’s disease. Preclinical studies explore USP5 inhibitors as potential anticancer agents, targeting its deubiquitinating activity to enhance proteasomal degradation of oncoproteins.