Ubiquitin-specific peptidase 51: A potential target in cancer progression and therapy

Ubiquitination, a reversible post-translational modification regulated by deubiquitinating enzymes, is pivotal for cancer initiation and progression. USP51, an emerging member of the USP family, plays essential roles in maintaining genomic stability and cell cycle homeostasis under physiological conditions, while its dysregulation drives multiple cancer-related biological processes. This review systematically synthesizes the substrate-dependent mechanisms underlying USP51's functional diversity across cancer types, its synergistic interactions with other USP family members via shared substrate targeting, and its dual potential as a cancer diagnostic/prognostic biomarker and therapeutic target. Core insights reveal that USP51 exerts context-specific effects through substrate diversity, with functional similarities to family members verifying intra-family synergism, which provides a novel mechanistic framework for USP51-related cancer research. Future research should focus on clarifying USP51's inter-family regulatory networks, validating targeted drugs in overcoming treatment resistance, and translating basic findings into precision oncology applications. This review constructs a USP51-centered molecular interaction landscape, highlighting its translational value in advancing cancer diagnosis and targeted therapy.