In adult conditional Nedd4-2−/− mice, we demonstrated that increased ENaC-mediated Na+/fluid absorption across airway epithelia, as previously shown in patients with cystic fibrosis and Scnn1b-Tg mice [6,30,31,32,33], results in airway surface liquid depletion and impaired mucociliary clearance [9]. The gene discussed is NEDD4L; the disease is cystic fibrosis.