NEDD4L and Liddle syndrome: Experiments performed in Xenopus oocytes or mammalian cultured cells that ectopically express ENaC reveal that unlike the ability of Nedd4-2 to induce removal of wild-type ENaC from the plasma membrane by ubiquitylation (likely linked to subsequent clathrin-mediated endocytosis [51]), Liddle syndrome mutations in the PY motif of β or γ ENaC severely attenuate this removal, leading to increased retention of mutant ENaC at the cell surface and to elevated channel activity [45,46,49] (Figure 2).