Usp16, also known as ubiquitin carboxyl-terminal hydrolase 16, is a deubiquitinase with diverse functions. It is involved in multiple pathways such as the KEAP1/Nrf2 signaling pathway, and plays a role in processes like histone modification, metabolism regulation, and cell cycle progression. Genetic models, especially KO/CKO mouse models, are crucial for studying its functions [1-3, 6].

In a HSCs-specific FGF18 deletion mouse model, FGF18 alleviated hepatic ischemia-reperfusion injury by reducing Usp16 levels, which increased KEAP1 ubiquitination and activated Nrf2 [1]. Oocytes lacking Usp16 due to conditional knockout had defects in zygotic genome activation, suggesting Usp16-mediated histone H2A lysine-119 deubiquitination is essential during oocyte maturation [2]. T cell-specific Usp16 knockout mice showed reduced severity of experimental autoimmune encephalitis and inflammatory bowel disease, indicating that Usp16-mediated deubiquitination of calcineurin A controls peripheral T cell maintenance [3].

In conclusion, Usp16 is essential for various biological processes including hepatic protection, oocyte maturation, and T-cell maintenance. The KO/CKO mouse models have been instrumental in revealing its role in hepatic ischemia-reperfusion injury, zygotic genome activation, and autoimmune diseases, providing insights into potential therapeutic targets for these conditions.