Usp16, also known as ubiquitin carboxyl-terminal hydrolase 16, is a deubiquitinase with multiple functions. It participates in various signaling pathways, such as the KEAP1/Nrf2 pathway, and is involved in important biological processes like metabolism regulation, cell cycle progression, and histone modification, which are crucial for normal cellular functions and development [1,2,3,4]. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying Usp16.

In a CKO mouse model where HSCs-specific FGF18 was deleted, it was found that the lack of FGF18-mediated reduction of Usp16 led to increased Usp16 levels, which in turn decreased the ubiquitination of KEAP1 and inactivated Nrf2, aggravating hepatic ischemia-reperfusion injury (IRI), suggesting Usp16's role in this disease process [1]. In oocytes, conditional knockout of Usp16 did not affect their survival, growth, or meiotic maturation, but oocytes lacking Usp16 had defects in zygotic genome activation and developmental competence after fertilization, indicating Usp16's importance in this early developmental stage [3]. T-cell-specific Usp16 knockout mice showed reduced severity of experimental autoimmune encephalitis and inflammatory bowel disease, revealing Usp16's role in maintaining peripheral T-cell function and its potential as an immunosuppressive drug target in autoimmune diseases [5].

In summary, model-based research, especially using Usp16 KO/CKO mouse models, has revealed that Usp16 is essential in processes like hepatic IRI, oocyte-to-zygote transition, and peripheral T-cell maintenance. These findings contribute to understanding the mechanisms of related diseases, such as hepatic diseases, early embryonic development disorders, and autoimmune diseases, providing potential targets for treatment.