This sequence suggests that impaired mucociliary clearance is an early abnormality important in triggering the pathogenic cascade, likely by leading to repeated micro-injury and inflammation of the airway epithelium caused by inhaled irritants and pathogens that are retained in the lung, whereas dysregulated, hyperresponsive TGFβ signaling is an important subsequent event that drives and perpetuates pulmonary fibrosis once epithelial micro-injury has been established in conditional Nedd4-2−/− mice. This evidence concerns the gene NEDD4L and pulmonary fibrosis.