USP4

Ubiquitin Specific Peptidase 4 (USP4) is a deubiquitinating enzyme that plays a critical role in regulating protein stability and signaling pathways by removing ubiquitin chains from target substrates^[1]. USP4 has been implicated in various cellular processes, including DNA damage response, cell cycle regulation, and apoptosis, highlighting its importance in maintaining genomic integrity^[2]. It is known to interact with key regulators such as p53 and SMAD proteins, modulating their activity and half-life through deubiquitination^[1]. In the context of cancer, USP4 acts as both a tumor suppressor and an oncogene depending on the cellular environment and substrate specificity, underscoring its dual functional nature^[3]. Recent studies have demonstrated that USP4 regulates TGF-β signaling by stabilizing SMAD4, thereby influencing epithelial-mesenchymal transition (EMT) and metastasis^[1]. Furthermore, USP4 has been linked to neurodegenerative diseases due to its involvement in the degradation of misfolded proteins via the ubiquitin-proteasome system^[4]. Its distinct substrate selectivity and catalytic mechanism differentiate it from other members of the USP family, particularly USP7 and USP10, which share structural similarities but exhibit divergent biological roles^[5]. Research tools such as USP4-specific inhibitors and knockout models are emerging, enabling more precise investigation into its physiological and pathological functions^[3].