USP34 is a cysteine-type deubiquitinase that regulates protein stability across multiple cellular pathways with significant implications for cancer and developmental biology. As a ubiquitin hydrolase, USP34 removes conjugated ubiquitin from target proteins, stabilizing key regulatory molecules including AXIN1, AXIN2, Pin1, SOX2, and β-catenin 1. In glioma stem cells, USP34-mediated deubiquitination and stabilization of Pin1 promotes isomerization of the SUMO E2 enzyme Ubc9, leading to hypersumoylation that supports cancer cell maintenance 2. USP34 promotes survival in pancreatic cancer by stabilizing protein kinases AKT and PKC, enhancing cell proliferation and migration while conferring resistance to apoptosis 3. In cervical cancer, USP34 upregulates Pin1 via SUMOylation, which subsequently inhibits the cGAS-STING pathway and suppresses ferroptosis, thereby promoting tumor progression 4. Similarly, in laryngeal squamous cell carcinoma, USP34 stabilizes the stemness factor SOX2, promoting drug resistance 5. Beyond oncology, USP34 enhances osteogenic pathways by stabilizing β-catenin and Smad1/RUNX2 6, and macrophage-expressed USP34 interacts with ATM to limit CD8+ T cell-mediated autoimmunity in vitiligo 7. USP34 mutations are associated with developmental defects including agenesis of the corpus callosum 8.