Pask, also known as Per-Arnt-Sim Kinase and proline-alanine-rich Ste20-related kinase (SPAK), is an evolutionarily-conserved nutrient-responsive protein kinase. It regulates multiple biological processes including lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. It is involved in pathways such as those related to insulin secretion, blood glucose regulation, and also has connections with nutrient sensors like AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (m-TOR) [1,3].

Pask knockout (PASK-/-) mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, suggesting Pask may be a target for metabolic syndrome treatment [1]. Genetic or pharmacological inhibition of Pask in mice upregulated Pax7 expression, reduced stem cell heterogeneity, and blocked myogenesis in vitro and muscle regeneration in vivo, indicating its role in muscle-related processes [2]. In addition, overexpression of a kinase-inactive, dominant-negative Pask mutant in HEK cells drastically reduced the activation of the Na-K-Cl cotransporter (NKCC1), showing its involvement in ion-transport regulation [4].

In conclusion, Pask plays crucial roles in metabolic regulation, muscle-related processes, and ion-transport regulation. Studies using Pask KO mouse models have provided valuable insights into its functions in metabolic syndrome and muscle-related diseases, highlighting its potential as a therapeutic target for these conditions.