The role of USP19 in human diseases: from molecular function to clinical relevance.

USP19 is an important member of the ubiquitin-specific protease (USP) subfamily within the deubiquitinase superfamily. It primarily regulates protein stability, subcellular localization, and signaling pathway activity by specifically removing ubiquitin modifications from substrate proteins, and it is widely involved in the regulation of cellular physiological homeostasis and various pathological processes. USP19 shows aberrant expression and functional dysregulation in multiple malignancies, participating in the regulation of tumor proliferation, metastasis, apoptosis, immune evasion, and chemoresistance by targeting key molecules such as c-Myc, p53, PD-L1, MGMT, and PARK7. Additionally, it regulates inflammatory responses, immune responses, viral infections, and non-neoplastic diseases such as liver injury, fibrosis, and neurodegeneration. Mechanistic research on USP19 has expanded considerably, and its key substrates and signaling pathways have become potential targets for pharmacological intervention; small-molecule modulators and the development of targeted strategies remain at the preclinical stage. USP19 displays disease-specific expression patterns across different tissues: it is aberrantly overexpressed in most tumors and is closely associated with poor patient prognosis, whereas in certain tumors and non-neoplastic diseases it shows low expression or a protective upregulation. This article systematically summarizes the molecular characteristics, physiological functions, disease-related mechanisms, and clinical translational potential of USP19, to provide a comprehensive overview for its use as a novel diagnostic biomarker, prognostic stratification tool, treatment response predictor, and direct drug target.