The serum and glucocorticoid inducible kinase 1 (SGK1) is expressed following cell stress including cell shrinkage and following exposure to several hormones including gluco- and mineralocorticoids. It is activated by insulin and growth factors via phosphatidylinositol-3-kinase, 3-phosphoinositide dependent kinase PDK1 and mammalian target of rapamycin mTOR. SGK1 enhances the activity of several renal ion channels (e.g. ENaC, TRPV5, ROMK, KCNE1/KCNQ1, ClCKb), carriers (e.g. NHE3, NKCC2, NCC, SGLT1, EAAT3), and the Na+/K+ ATPase. SGK1 contributes to Na+ retention and K+ elimination of the kidney as well as to the mineralocorticoid stimulation of salt appetite. SGK1 accounts for the stimulating effect of insulin on renal tubular salt reabsorption and SGK1-deficient mice are resistant against the hypertension during combined salt excess and hyperinsulinemia. The mice are further resistant against the hypertensive effect of glucocorticoids. During combined mineralocorticoid and salt excess, blood pressure increases initially to a similar extent in SGK1 knockout mice and wild type mice, but continues to increase further in wild type mice but not in SGK1 knockout mice. The SGK1 knockout mice are protected against renal and cardiac fibrosis following combined mineralocorticoid and salt excess. SGK1-dependent renal salt retention further facilitates the development of edema following administration of PPARγ agonists, in nephritic syndrome or during ascites formation. SGK1 expression is low in proximal renal tubules of normal animals, but upregulated by hyperglycemia. In diabetes SGK1 thus stimulates proximal renal tubular glucose reabsorption. In humans, a certain SGK1 gene variant (combined polymorphisms in intron 6 [I6CC] and exon 8 [E8CC/CT]) is associated with moderately enhanced blood pressure. The SGK1 gene variant is common, affecting 3-5 % of the Caucasian population and some 10% of an African population. The gene variant sensitizes the individuals to the hypertensive effects of hyperinsulinemia, to obesity and to development of type II diabetes. The obesity is at least in part due to stimulation of intestinal SGLT1. SGK1 further stimulates coagulation. Accordingly, SGK1 is a signaling element predisposing to the development of metabolic syndrome or syndrome X, a condition characterized by the coincidence of essential hypertension, procoagulant state, obesity, insulin resistance and hyperinsulinism. Moreover, maternal SGK1 is required for fetal programming of hypertension, i.e. the hypertension in offspring following stress of the mother. SGK1 further participates in the regulation of a wide variety of extrarenal functions. The phenotype of the SGK1 knockout mouse is, however, mild and the lack of SGK1 becomes only apparent under certain stress conditions.