USP19 is a deubiquitinating enzyme that regulates protein stability across multiple cellular pathways with significant disease implications. As a cysteine-type deubiquitinase, USP19 removes ubiquitin moieties from target proteins to prevent their proteasomal degradation 1. Its functions are highly context-dependent: in cancer, USP19 promotes hepatocellular carcinoma by stabilizing SOAT1 to enhance cholesterol esterification 1, stabilizes YAP to facilitate HCC progression 2, and stabilizes PD-L1 to suppress T-cell-mediated antitumor immunity in colorectal cancer 3. Conversely, in pancreatic cancer, USP19 acts as a tumor suppressor by stabilizing NEK9, which inhibits mTORC1 signaling and promotes autophagic cell death 4. USP19 also protects against ferroptosis by deubiquitinating SLC7A11 in liver transplantation contexts 5 and stabilizes TRAF2 to prevent doxorubicin-induced cardiotoxicity by preserving NF-κB survival signaling 6. In metabolic disorders, USP19 in adipocytes and hepatocytes promotes hyperglycemia and non-alcoholic fatty liver disease 7, while it enhances colorectal carcinogenesis by stabilizing ME1 to promote lipogenesis 8. These divergent roles highlight USP19's importance as both a potential therapeutic target and biomarker across multiple cancer types and metabolic diseases.