The epithelial sodium channel ENaC expressed in the aldosterone-sensitive distal nephron (ASDN), represents the major pathway for Na+ absorption. The importance of the ASDN in maintaining extracellular electrolyte and water balance is nicely demonstrated by the elucidation of the genetic basis of rare monogenic forms of hypertension, due to mutations in the genes coding for ENaC. ENaC belongs to a family of ion channels that includes the neuronal acid-sensing ion channels (ASIC1, ASIC2, ASIC3) in mammals, touch-activated ion channels called degenerins in C. elegans, and a variety of homologs in drosophila, mollusks. ENaC is a highly Na+ selective channel made of three α, β, and γ homologous subunit. The α subunit is absolutely required for channel activity, whereas the β and γ are necessary for maximal channel expression and activity at the cell surface. New insights in ENaC structure came from the resolution of the 3D structure of a channel homolog, the ASIC1a channel. Based on a homology models each ENaC subunit is composed of 2 transmembrane α helices, a large extracellular loop that makes more than half of the mass of the protein, the intracellular N- and C- termini facing the intracellular side. From structure-function studies, the pore region of ENaC is lined by the second transmembrane α helix that contains an extracellular activation site, the amiloride binding site, and the selectivity filter. The N- and C-termini are accessible by intracellular ligands that directly target functional domains controlling channel gating. The crystal structure of the ASIC1a channel is a homotrimeric channel. Several evidences are consistent with a tetrameric structure of ENaC composed of 2α, 1β and 1γ subunit. Purification of the functional complex of ENaC shows evidences that ENaC is made of more than 1α, 1β, 1γ subunits. The crystal structure of ASIC1a provides high resolution informations of the subunit structure of the member of ENaC-deg channel family. The question that remains to be solved is the subunit architecture of ENaC as to whether the channel is a trimer or a tertramer. This question is essential for our understanding of ENaC function at the molecular level.