The epithelial sodium channel (short: ENaC, also: amiloride-sensitive sodium channel) is a membrane-bound ion-channel that is selectively permeable to Na⁺ ions and that is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. It is involved primarily in the reabsorption of sodium ions in the collecting ducts of the kidney's nephrons.

The apical membranes of many tight epithelia contains sodium channels that are characterized primarily by their high affinity for the diuretic blocker amiloride. These channels mediate the first step of active sodium reabsorption essential for the maintenance of body salt and water homeostasis. In vertebrates, the channels control reabsorption of sodium in kidney, colon, lung and sweat glands; they also play a role in taste perception.

ENaC is located in the apical membrane of polarized epithelial cells in particular in the kidney (primarily in the distal tubule), the lung, and the colon. Epithelial sodium channels facilitate Na⁺ reabsorption across the apical membranes of epithelia in the distal nephron, respiratory and reproductive tracts and exocrine glands, and hence they have a role in fluid volume homeostasis, osmolarity and arterial blood pressure regulation.

It plays a major role in the Na⁺- and K⁺-ion homeostasis of blood and epithelia and extraepithelial fluids by resorption of Na⁺-ions. The activity of ENaC in colon and kidney is modulated by the mineralcorticoid aldosterone. It can be blocked by either triamterene or amiloride, which are used medically to serve as diuretics. In the kidney, it is inhibited by atrial natriuretic peptide, causing natriuresis and diuresis.

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