PASK (PAS domain containing serine/threonine kinase) is a nutrient-responsive serine/threonine protein kinase that functions as an energy sensor regulating glucose and lipid metabolism 1. The kinase phosphorylates key metabolic substrates including glycogen synthase (GS), modulating its activity to regulate glycogen synthesis in response to nutrient availability 1. PASK operates in pancreatic islet cells, influencing insulin secretion from β-cells and glucagon regulation in α-cells through its effects on glucose metabolism 1. Additionally, PASK is expressed in pancreatic islet endothelial cells where it functions as a metabolic gene regulating vascular-specific signatures 2. The kinase also participates in mitochondrial respiration regulation and may enhance protein translation efficiency through phosphorylation of elongation factors 1. Clinically, PASK appears relevant to metabolic syndrome pathogenesis. PASK knockout mice demonstrate protection against obesity, hepatic triglyceride accumulation, and insulin resistance when challenged with high-fat diet, suggesting PASK inhibition may provide therapeutic benefits 1. This positions PASK as a potential therapeutic target alongside established metabolic sensors like AMPK and mTOR for treating metabolic dysfunction 1. However, additional research is needed to fully elucidate PASK's role in human metabolic disease and validate its therapeutic potential.