Because mucociliary clearance is an important defense mechanism of the airways and its failure results in chronic epithelial injury and inflammation, these data support mucociliary dysfunction as an important extracellular pathogenic process that triggers airway remodeling and pulmonary fibrosis in conditional Nedd4-2−/− mice, as recently suggested in an independent model where mucociliary clearance was reduced due to transgenic overexpression of Muc5b and shown to be associated with more severe and persistent bleomycin-induced pulmonary fibrosis in mice6,34. The gene discussed is NEDD4L; the disease is pulmonary fibrosis.