Usp33, also known as VDU1, is a deubiquitinating enzyme. It plays crucial roles in multiple biological processes by deubiquitinating various substrate proteins, influencing pathways such as mitophagy, cancer-related signaling, and DNA damage response [1,2,3,4]. Its abnormal regulation is associated with diseases like Parkinson's disease and several types of cancers, highlighting its biological importance. Genetic models, such as gene knockout mouse 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 [4]. In gerbils, knockdown of Usp33 inhibited hepatic stellate cell activation and glycolysis in nonalcoholic fatty acid disease-associated fibrosis, while overexpression had the opposite effect, suggesting its role in this fibrotic process [5].

In conclusion, Usp33 is an important deubiquitinating enzyme. Model-based research, especially through gene knockout mouse models, has revealed its diverse functions in cancer, fibrosis, and DNA damage response. Understanding Usp33's functions can provide potential therapeutic targets for diseases such as Parkinson's disease, various cancers, and non-alcoholic fatty acid disease-associated fibrosis.