The DEG/ENaC family consists of Na⁺ selective channels. They are characterized by 2 transmembrane domains with a large extracellular loop, important for channel activity and intracellular N-and C-termini which are important for channel gating and for interacting with regulatory proteins respectively^1,2.

ENaC is localized to the apical side of polarized epithelial cells like those in the kidney, lung, and distal colon and is responsible for maintaining proper Na⁺ balance. This channel is formed by oligomerization of three subunits, α, β, and γ usually with the α₂β₁γ₁ combination^2,3. In addition, the α subunit which is essential for channel activity undergoes phosphorylation in its C-terminal by SGK1 (serum and glucocorticoid-induced kinase 1) which is known to activate the channel at the plasma membrane⁴.

Pseudohypoaldosteronism type 1 (PHA-1) has an early onset and is depicted by severe dehydration, hyponatremia and hyperkalemia⁵. One form of the pathology is characterized by mutations in α, β, and γ subunits⁵. The severity of the diseases depends on the loss of activity of the channel².