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 involved in metabolic regulatory mechanisms, playing a crucial role in maintaining cellular metabolic homeostasis. SnRK participates in multiple signaling pathways, such as those related to metabolism, DNA damage response (DDR), and autophagy, and is important for various biological processes including plant growth, development, stress responses, and mammalian cardiovascular function and lipid homeostasis [1,2,3,4]. Genetic models like knockout (KO) and conditional knockout (CKO) mice are valuable tools for studying its functions.

In cardiac-specific Snrk-/-mice, transaortic banding leads to worse cardiac function, increased cardiac hypertrophy, and elevated DDR marker pH2AX, indicating SnRK's role in cardiac hypertrophy and DNA damage [1]. In MAFLD, SnRK-deficient mice show fatty acid oxidation damage and persistent liver lipid accumulation, and pharmacological inhibition of the mTOR pathway in these mice restores autophagy and improves lipid accumulation, suggesting SnRK's importance in liver lipid homeostasis [3]. Conditional knockout of Snrk in mouse cardiomyocytes causes atrial fibrosis and heart failure, with Snrk knockdown cells showing more TGFβ1 secretion, demonstrating its role in regulating cardiac fibrosis [5]. In Snrk global heterozygous knockout and endothelial cell-specific Snrk deletion mice, retina angiogenesis and neovessel formation after hindlimb ischemia are suppressed, revealing SnRK's role in angiogenesis [6]. Also, cardiomyocyte-specific Snrk knockout in adult mice leads to heart failure, increased inflammation, and fibrosis, highlighting SnRK as a cardiomyocyte-specific repressor of cardiac inflammation and fibrosis [7].

In conclusion, SnRK is a key regulator in multiple biological processes. Studies using SnRK KO/CKO mouse models have revealed its significance in diseases like cardiac hypertrophy, MAFLD, cardiac fibrosis, and angiogenesis, as well as its role in maintaining cardiac function by suppressing inflammation. These findings provide insights into potential therapeutic strategies targeting SnRK for related diseases.