Senp1, short for Sentrin/SUMO-specific protease 1, is a cysteine protease that processes precursor SUMO protein into its mature form and deSUMOylates target proteins. It is involved in multiple physiological and pathological processes, with its functions often linked to pathways like those related to protein modification and regulation of cellular metabolism, apoptosis, and inflammation [1,2,3,4,5,6,7,8,9,10]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in understanding its role.

In hepatocyte-specific SENP1-knockout mice, there is a spontaneous development of non-alcoholic steatohepatitis (NASH)-related phenotypes in a RIPK1 kinase-dependent manner, indicating SENP1's role in preventing NASH by suppressing RIPK1-driven apoptosis and inflammation [2]. In T cell memory development, glucose limitation activates AMPK-coupled SENP1-Sirt3 signalling in mitochondria. SENP1-Sirt3 signalling promotes T cell memory development through enhancing Sirt3 deacetylase activity, leading to mitochondrial fusion [5]. In pressure overload-induced cardiac remodelling, cardiac-specific SENP1 knockdown exacerbates cardiac hypertrophy, while overexpression attenuates remodelling and dysfunction by inhibiting STAT3 signalling [8].

In conclusion, Senp1 is essential in various biological processes, including metabolism, apoptosis, and inflammation. KO/CKO mouse models have revealed its significant roles in diseases such as NASH, T cell-related immune responses, and cardiac remodelling. Understanding Senp1's functions through these models provides valuable insights into disease mechanisms and potential therapeutic targets.