Ubiquitin-specific protease 19 (USP19)

Ubiquitin-specific protease 19 (USP19) is a modular deubiquitinating enzyme belonging to the ubiquitin-specific proteases (USP) family, which removes ubiquitin molecules from substrate proteins to regulate their stability, activity, and degradation. Human USP19 is encoded by the USP19 gene and exists in several isoforms due to alternative splicing, with some forms anchored to the endoplasmic reticulum membrane while others are cytoplasmic. USP19 is implicated in protein quality control, especially in ER-associated degradation (ERAD), autophagy, and the regulation of muscle mass. It plays key roles in the regulation of crucial cellular pathways, including hypoxia, apoptosis, immune signaling, and tumorigenesis, by modulating ubiquitination states of proteins such as HIF-1α, Beclin-1, p27^Kip1, c-IAPs, and others. Increasing evidence links USP19 to oncogenic processes, neurodegeneration (through protein aggregation), and immune responses. As of 2024, USP19 is considered an emerging therapeutic target, especially in oncology and proteinopathy-related neurodegenerative diseases, but no specific clinical drugs have been approved against it[1][2][3][4].

Other names

Ubiquitin carboxyl-terminal hydrolase 19KIAA0891ZMYND9Deubiquitinating enzyme 19Ubiquitin thioesterase 19Zinc finger MYND domain-containing protein 9

Inhibition of USP19 would increase ubiquitination and proteasomal degradation of its substrates, affecting processes such as tumorigenesis, autophagy, and protein aggregation[1][2][4].