Usp13, short for ubiquitin-specific protease 13, is a deubiquitination (DUB) enzyme. It is involved in numerous cellular processes such as mitochondrial energy metabolism, autophagy, DNA damage response, and endoplasmic reticulum-associated degradation (ERAD) by regulating the deubiquitination of various key substrate proteins [1]. Dysregulation of Usp13 can lead to the development of many diseases, especially malignant tumors [1]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In kidney cancer, depletion of Usp13 led to decreased cell proliferation and down-regulation of ZHX2 protein, indicating its role in tumorigenesis [2]. In lung squamous cell carcinoma, overexpressing Usp13 in a mouse model (KPU) showed that it drives lineage plasticity in club cells and up-regulates squamous programs [3]. In non-small cell lung cancer, elevated Usp13 promotes metastasis, and its inhibitor can suppress metastasis in vitro and in vivo [4]. In gastric cancer, suppression of Usp13 led to cell cycle arrest and inhibited cell proliferation, and its depletion in nude mice suppressed tumor growth [6]. In gastrointestinal stromal tumors, an inhibitor of Usp13 caused decay of ATG5 and enhanced the treatment efficacy of imatinib in murine xenograft models [5]. In age-related lung fibrosis, Usp13-deficient aged mice had impaired autophagic activity and increased vulnerability to bleomycin-induced fibrosis [7].

In conclusion, Usp13 is a crucial regulator in multiple biological processes. Through model-based research, especially KO/CKO mouse models, it has been shown to play significant roles in cancer and age-related lung fibrosis. Understanding Usp13 can provide potential therapeutic targets for these diseases.