Genetic analyses of representative familial hereditary hypertension, known as Liddle syndrome, showed that the Proline-Tyrosine (PY) motif in the C terminus of ENaCs are commonly mutated, resulting in impaired protein-protein interactions with the Nedd4L Tryptophan-Tryptophan (WW) domain [22]. Here, NEDD4L is linked to Liddle syndrome.