The epithelial sodium channel (ENaC) is made up of three subunits (αβγ or δβγ), and the predominant ENaC consists of αβγ subunits, regulating the homeostasis of fluids and sodium ions. ENaC controls blood pressure and volume by reabsorbing fluid from the kidneys into the blood. ENaC also maintains fluids in the colon and the normal airway surface in the lung and other epithelial cells. Investigations on ENaC showed that it is also found in non-epithelial cells and tissues like neurons and endothelial cells of blood vessels. Recent investigations have demonstrated that ENaC is regulated by various proteins (SGK-1, NEDD4-2, AMPK, mTORC2, WNKs, proteases, and AKT), ions (Na+), hormones (vasopressin, aldosterone, and glucocorticoids), and even by post-translational modifications (acetylation, glycosylation, palmitoylation, phosphorylation, and de-ubiquitylation). From a clinical perspective, abnormal expression of ENaC gives rise to various clinical conditions like Liddle syndrome (hereditary hypertension), pseudohypoaldosteronism type-1, and cystic fibrosis (polymorphism in ENaC). This review emphasizes the distribution, structure, and function of ENaC, as well as its clinical importance. We also shed light on the aspects of ENaC regulations and clinical conditions developed owing to ENaC alterations.
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