SnRK, short for sucrose non-fermenting 1-related kinase, is a serine/threonine kinase and a member of the AMP-activated protein kinase (AMPK) family. It is crucial for maintaining cellular metabolic homeostasis, participating in various metabolic regulatory mechanisms. In plants, the SnRK family is highly conserved and involved in multiple signaling pathways related to growth, development, and stress responses. In mammals, it is associated with pathways like mTOR-autophagy, and is important for physiological processes such as cardiac function, angiogenesis, and liver lipid homeostasis [2,3,4,6]. Genetic models, especially knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying SnRK's functions.

In KO mouse models, cardiac-specific Snrk-/-mice display worse cardiac function, cardiac hypertrophy, increased DNA damage, and chromatin compaction in response to transaortic banding. SnRK interacts with DSTN, an F-actin depolymerizing factor, and this interaction fine-tunes actin polymerization to maintain proper cardiomyocyte nuclear shape [1]. Mice deficient in SNRK exhibit fatty acid oxidation damage and persistent liver lipid accumulation, while pharmacological inhibition of the mTOR pathway in these mice restores autophagy and improves lipid accumulation [3]. Conditional knockout of Snrk in mouse cardiomyocytes leads to atrial fibrosis and heart failure, as SNRK expression in atria is associated with lower levels of pro-fibrotic protein TGFβ1 [5]. Also, Snrk global heterozygous knockout mice and mice with endothelial cell-specific Snrk deletion show suppressed retina angiogenesis and impaired perfusion recovery in ischemic hindlimbs [6]. In addition, 4-month-old adult mice with cardiomyocyte-specific Snrk knockout show rapid decline in cardiac systolic function, increased inflammation, and fibrosis upon angiotensin II infusion [7].

In conclusion, SnRK plays essential roles in multiple biological processes. In the context of diseases, SnRK is involved in cardiac hypertrophy, liver lipid-related disorders, atrial fibrosis, and angiogenesis-related pathologies. The use of Snrk KO and CKO mouse models has significantly advanced our understanding of its functions in these disease-related processes, providing potential therapeutic targets for treating cardiovascular diseases, metabolic-related fatty liver disease, and other related conditions.