SIRT2, a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, is the only sirtuin predominantly in the cytoplasm, also present in mitochondria and the nucleus. It plays crucial roles in multiple biological processes like cell differentiation, homeostasis, aging, and immunity, and is involved in pathways such as cGAS-STING and Wnt/β-catenin [2,3,5]. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying its functions.

In KO mouse models, liver-specific SIRT2 deficiency inhibits osteoclastogenesis and alleviates bone loss in osteoporosis models, revealing its role in liver-bone crosstalk [1]. Sirt2 knockout in male C57BL/6J mice exaggerates cardiac hypertrophy and fibrosis in aging-related and angiotensin II-induced pathological cardiac hypertrophy, while cardiac-specific SIRT2 overexpression protects against these conditions [4]. In SIRT2-deficient mice, there are impairments in intestinal cell proliferation and differentiation, and a decrease in SIRT2 expression is seen in intestinal mucosa from IBD patients [5]. Also, Sirt2-deficient mice show exacerbated hypertensive renal injury due to hyperacetylation of septin4-K174 [6].

In conclusion, SIRT2 has diverse biological functions. Model-based research, particularly KO mouse models, has shown its significance in diseases such as osteoporosis, cardiac hypertrophy, IBD, and hypertensive nephropathy. Understanding SIRT2 can potentially lead to new therapeutic strategies for these diseases.