Ubiquitin specific peptidase 24 (USP24)

Ubiquitin specific peptidase 24 (USP24) is a large (2620 amino acids) deubiquitinating enzyme belonging to the ubiquitin-specific protease (USP) family of cysteine proteases[1][2]. It removes ubiquitin from specific protein substrates, thereby stabilizing them and affecting a variety of cellular processes, including DNA damage response (directly stabilizing p53), protein homeostasis, autophagy (through Beclin1 stabilization), immune regulation (by stabilizing PD-1), histone modification, and maintenance of genome stability[1][2][3][5]. USP24 has been implicated in cancer progression and prognosis, particularly in hepatocellular carcinoma, gastric, and bladder cancers, as well as in neurodegenerative diseases like Parkinson's disease[1][3][7]. Its modulation is being explored experimentally in oncology and as a possible immune checkpoint regulatory target[5][6]. Drugs targeting USP24 are in early stages and are primarily experimental.

Other names

Ubiquitin carboxyl-terminal hydrolase 24KIAA1057Deubiquitinating enzyme 24Ubiquitin thioesterase 24Ubiquitin-specific-processing protease 24Ubiquitin specific protease 24Ubiquitin thiolesterase 24

Inhibitors block deubiquitinase activity, leading to increased degradation of USP24 substrates such as p53, Beclin1, or PD-1 proteins[4][6]. By inhibiting USP24, autophagy or ferroptosis can be modulated as therapeutic strategies in cancer[3][6].