Sodium and water homeostasis is regulated by the activity of the epithelial sodium channel (ENaC), a crucial factor for the physiology and well-being of the human body. In particular the ENaC is the main receptor candidate for salty taste. Nowadays, the mechanisms and behaviour of this receptor are not fully known, and their transmembrane and cytosolic domains have not been resolved yet. Despite reduced knowledge of the molecular mechanisms of receptor activation, one of the most accredited hypotheses relates the so-called cleavage mechanism with a more active state of ENaC, representing, nowadays, the main actor in the gating mechanism of the receptor.