Usp25, or ubiquitin-specific peptidase 25, is a deubiquitinating enzyme that plays crucial roles in various biological processes. It is involved in pathways such as NF-κB, MAPK, and Wnt/β-catenin, regulating protein function, localization, and degradation. Genetic models like gene knockout (KO) mice have been essential in studying its functions, which are significant for normal physiological and pathological conditions [1-10].

In KO mouse models, Usp25 deficiency aggravated cardiac hypertrophy and dysfunction in response to Ang II and transverse aortic constriction, as it normally stabilizes SERCA2a by deubiquitination [1]. In cerebral ischemic stroke, Usp25-deficient mice had more severe injury due to increased microglia-mediated neuroinflammation [2]. In Alzheimer's disease-related models, genetic deletion of Usp25 reduced amyloid deposition [3]. In hepatocellular carcinoma, knocking out Usp25 inhibited tumor growth and distant metastasis in vivo [4]. In male mice with acetaminophen-induced liver injury, Usp25 inactivation attenuated liver injury [5]. Usp25 knockout mice showed increased seizure susceptibility [6]. In colon cancer, USP25-deficient cells were more sensitive to chemotherapy [7]. In diabetic nephropathy, ablation of Usp25 aggravated diabetes-induced renal dysfunction and fibrosis [8]. In acute pancreatitis models, Usp25 deficiency in macrophages exacerbated pancreatic and lung injury [9]. In IgG4-related disease, reduced Usp25 expression led to increased fibrosis and inflammation [10].

In conclusion, Usp25, as a deubiquitinating enzyme, is involved in multiple biological processes and disease conditions. The use of KO mouse models has revealed its roles in cardiac, neural, cancer, and inflammatory-related diseases, highlighting its potential as a therapeutic target in these areas.