Mst1, short for mammalian sterile 20-like kinase 1, belongs to the serine/threonine protein kinase superfamily. It is a key regulator in multiple biological processes, being involved in inflammation, immunity, and the Hippo pathway. In the context of inflammation, it can aggravate inflammatory injury via MST1-JNK, MST1-mROS, MST1-Foxo3, and NF-κB pathways, and is associated with regulatory factors like TNF-α, MIEF1, and LPS [1]. In immunity, it balances immune activation and tolerance through MST1/2-Rac, MST1-Akt1/c-myc, MST1-Foxos, MST1-STAT, Btk pathways, and LFA-1 regulation [1].

In vivo studies using KO/CKO mouse models have provided valuable insights into Mst1's functions. For example, in an atherosclerosis model, EC-specific Mst1 deficiency on an ApoE-/-background (Mst1iECKOApoE-/-) mice were used. It was found that phosphorylation of endothelial Mst1 was inhibited in oscillatory shear stress-exposed regions, and overexpression of wild-type Mst1 reversed disturbed flow-caused EC activation and atherosclerosis, suggesting Mst1 suppresses disturbed flow-induced atherosclerosis [2]. In a non-alcoholic fatty liver disease (NAFLD) model, genetic ablation of Mst1 in mice attenuated HFD-mediated hepatic injury, as Mst1 knockdown reversed Parkin-related mitophagy which protected mitochondria and hepatocytes against HFD challenge, indicating Mst1 may contribute to NAFLD via disrupting Parkin-related mitophagy [3].

In conclusion, Mst1 plays essential roles in inflammation, immunity, and atherosclerosis, NAFLD. The use of Mst1 KO/CKO mouse models has revealed its functions in these disease-related biological processes, providing potential therapeutic targets for treating these diseases. [1-3]