Ubiquitin carboxyl-terminal hydrolase 38 (USP38)

Ubiquitin carboxyl-terminal hydrolase 38 (USP38) is a member of the USP family of deubiquitinating enzymes. It catalyzes the removal of ubiquitin chains from various substrates, including LSD1, HDAC1/HDAC3, TBK1, MYC, and IL-33R, thus influencing their stability and activity[1][3][5]. USP38 regulates critical cellular processes such as DNA repair, cell cycle progression, apoptosis, immune signaling, protein degradation, and epigenetic modulation. Its abnormal expression and function have been implicated in cancer progression, inflammation, cardiovascular disease, asthma, and infection. USP38's dual roles—as either a tumor suppressor or promoter—depend on cellular context and interacting partners. While considered a promising therapeutic target, there are currently no selective drugs approved for USP38, and development is complicated by its complex biological functions and risk of systemic effects[3][4][6].

Other names

Ubiquitin specific peptidase 38USP38KIAA1891Deubiquitinating enzyme 38Ubiquitin thioesterase 38Ubiquitin-specific-processing protease 38UCH38

Drugs targeting USP38 (hypothetically) would inhibit its deubiquitinase activity, thereby altering the stability and activity of target proteins such as LSD1, HDAC1/3, KLF5, c-Myc, METTL14, and HIF-1α. Disruption of USP38-mediated deubiquitination could affect cell proliferation, migration, apoptosis, and immune signaling.