USP11 is a cysteine-type deubiquitinase localized to the cytosol and nucleus that regulates protein stability through selective deubiquitination of target substrates 1. Mechanistically, USP11 removes K48-linked and K63-linked polyubiquitin chains from diverse substrates including Sirt3, AR, c-Myc, SREBF1, Nrf2, HOXC5, PRDX2, and VEGFR2, stabilizing these proteins and promoting their nuclear translocation or transcriptional activity 12345. USP11 displays context-dependent pathological roles across multiple disease states. In neurodegenerative disease, USP11 escapes X-inactivation and is elevated in females, where it promotes tau deubiquitination and acetylation, increasing tauopathy vulnerability and Alzheimer's disease risk in women 6. In cancers, USP11 overexpression drives oncogenic programs: in prostate cancer via AR/c-Myc upregulation 2, in hepatocellular carcinoma through SREBF1-mediated lipogenesis 3, in colorectal cancer via USP11/Nrf2 antioxidant feedback loops 4, and in bladder cancer through MYC stabilization and glycolysis 7. USP11 also promotes angiogenesis via PRDX2/c-MYC axis activation 5. Conversely, USP11 deletion protects against intervertebral disc degeneration by reducing ferroptosis 1 and supports spermatogenesis through HOXC5/WNT signaling 8. These findings position USP11 as a multifunctional deubiquitinase with therapeutic potential as both a target for cancer and neurodegeneration and a candidate for regenerative medicine applications.