NEDD4L and Hypertension: Each subunit has a highly conserved sequence at its carboxyl terminal, known as the PY motif, which binds to the ubiquitin ligase Nedd4-2 and causes the internalization of ENaC and degradation.[1] When the gene is mutated, the internalization and degradation of ENaC is dysfunctional, causing excessive Na + reabsorption, resulting in increased plasma volume and causing hypertension.