NEDD4L and Hypertension: Mutant ENaC, lacking the C‐terminal PY motif or containing a disrupted consensus PY motif due to missense mutations, possesses an increased sodium channel activity and membrane retention that results in hypertension in Liddle syndrome.101, 102, 103, 104 Similar to the structure of NEDD4, the other WW domain‐containing E3 ligase, NEDD4L, catalyzes ubiquitination and promotes cell surface ENaC degradation (Figure 6B),105 suggesting that both NEDD4 and NEDD4L have the similar role in regulating ENaC turnover.