Ubiquitin carboxyl-terminal hydrolase 53 (USP53)

Ubiquitin carboxyl-terminal hydrolase 53 (USP53) is a member of the USP family of deubiquitinating enzymes but is catalytically inactive due to a missing essential histidine in its active site[1][4]. Despite this, USP53 has significant physiological roles, especially in maintaining tight junction integrity in epithelial tissue and in regulating key cellular processes including apoptosis, nerve transmission, and bone remodeling[1][2][3][4][5]. USP53 interacts with tight junction proteins (notably TJP1 and TJP2), and its dysfunction is implicated in diseases such as progressive familial intrahepatic cholestasis (PFIC7), hearing loss, certain cancers, and bone disorders[1][3][4]. In bone tissue, USP53 positively regulates osteogenic differentiation, partly through the Wnt/β-catenin signaling pathway and interactions with FBXO31, making it a potential therapeutic target for bone regeneration and a diagnostic/prognostic marker for related diseases[2][1]. Loss or mutation of USP53 is linked to disease phenotypes in humans and animal models, including low bone mass, increased bone marrow adiposity, hearing impairment, liver dysfunction, increased tumor radioresistance, and abnormal fat metabolism[1][2][3][4]. No clinically approved drugs are currently known to directly target USP53, nor are there reported specific mechanism-of-action details for therapeutic modulators of USP53 at this time[3][5].

Other names

KIAA1350PFIC7ubiquitin-specific peptidase 53ubiquitin specific protease 53ubiquitin specific proteinase 53inactive ubiquitin carboxyl-terminal hydrolase 53inactive ubiquitin-specific peptidase 53