USP25 is a deubiquitinating enzyme that regulates protein stability through removal of ubiquitin chains, with diverse roles in cellular processes and disease pathogenesis. The enzyme exhibits substrate-specific deubiquitinase activity, removing both K48-linked ubiquitin chains (promoting protein stabilization) and K63-linked chains (modulating signaling pathways) 1234. USP25 functions through multiple mechanisms including stabilization of key regulatory proteins: it deubiquitinates SHLD2 to promote DNA repair via non-homologous end joining 2, stabilizes STAT6 to enhance macrophage M2 polarization 3, maintains KRAS protein levels in cancer cells 5, and removes K63-linked ubiquitin from TAB2 to inhibit neuroinflammation 4. Disease relevance includes roles in cancer progression, where USP25 promotes hepatocellular carcinoma through Wnt/β-catenin signaling 6 and maintains oncogenic KRAS signaling 5. Additionally, USP25 contributes to fibrosis development 13, platelet hyperreactivity during aging 7, and provides neuroprotection against ischemic stroke 4. Clinical significance is evidenced by its identification as a potential Parkinson's disease risk locus 8 and its therapeutic potential as a target for cancer treatment and other age-related pathologies.