USP19 is a deubiquitinating enzyme that regulates the degradation of various proteins such as RNF123, which stimulates CDKN1B ubiquitin-dependent degradation and impacts cell proliferation. It is required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. USP19 is important for regulating the expression and quality control of misfolded polyQ-expanded proteins. Additionally, USP19 decreases protein synthesis in atrophying skeletal muscle, represses myogenesis and regulates the transcription of major myofibrillar proteins. Because USP19 regulates and can inhibit muscle cell differentiation, it is a potential target of inhibition therapy as a means to increase post-injury muscle growth. Furthermore, USP19 deubiquinates a number of proteins including HDAC1 and HDAC2 that are pivotal for DNA repair and maintenance of chromosomal stability, and thus loss of USP19 is thought to contribute to genomic instability and to play a role in tumorigenesis. In immunohistochemistry of normal tissue, USP19 has cytoplasmic (endoplasmic reticulum) positivity in a majority of tissues throughout the body, with high expression in skeletal muscle. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; PLoS One. 2016 Jan 25;11(1):e0147515, PMID: 26808260; Mol Biol Cell. 2015 Mar 1;26(5):913-23, PMID: 25568336; Oncotarget. 2017 Jan 10; 8(2): 2197–2208, PMID: 27517492