USP10 deubiquitinase: Physiological function, diseases and therapeutic target (Review)

Ubiquitination is crucial for regulating diverse cellular functions, including protein degradation, cell cycle progression, signal transduction and gene expression. This intricate process is mediated by the ubiquitin proteasome system. Within this system, ubiquitin‑specific protease 10 (USP10) is a key member that, through its deubiquitinase activity, orchestrates multiple cellular processes, such as DNA damage repair, immune and inflammatory responses, environmental adaptation and autophagy. The biological activity and protein stability of USP10 are extensively regulated by post‑translational modifications, including PARylation, histone methylation and ubiquitination. Functionally, USP10 has a dual role in tumorigenesis: It can either promote or suppress cancer progression and metastasis by influencing oncogenic signaling pathways. Beyond cancer, USP10 has been implicated in the pathogenesis of cardiovascular and neurodegenerative diseases, as well as organ fibrosis, underscoring its broad physiological relevance. Decades of research have spurred the development of a range of USP10 inhibitors, such as Spautin‑1, P22077, HBX19818, Wu‑5 and D1. The present review provides a comprehensive overview of recent advances in understanding the role of USP10 in maintaining homeostasis and dissects the pathological mechanisms in human diseases. The review further highlights the potential of precise USP10‑targeted interventions as promising therapeutic strategies for disease prevention and treatment.