Usp33, also known as VDU1, is a deubiquitinating enzyme. It plays crucial roles in multiple biological processes by deubiquitinating key proteins, thus affecting various pathways [1-10]. It is involved in pathways like mitophagy, TGF-β signaling, and is associated with many diseases including cancer, non-alcoholic fatty acid disease-associated fibrosis [1,2,4]. Genetic models, such as gene knockout models, are valuable for studying its functions.

In a hepatocyte-specific Usp33 knockout mouse model, the mice were more sensitive to nitrosodiethylamine (DEN)-induced hepatocarcinogenesis, indicating that Usp33 has anti-tumour activity via regulating p53 stability and activity [3]. In addition, knockdown of Usp33 in gerbils with non-alcoholic fatty acid disease-associated fibrosis inhibited hepatic stellate cell activation and glycolysis [4].

In conclusion, Usp33 is a significant deubiquitinating enzyme. Through model-based research, especially KO mouse models, it has been shown to play important roles in processes like mitophagy, cancer progression, and fibrosis. These findings contribute to understanding disease mechanisms in areas such as Parkinson's disease, various cancers, and non-alcoholic fatty acid disease-associated fibrosis, potentially providing new therapeutic targets.