In this report, we demonstrate that NEDD4-2 is reduced in lung epithelial cells of patients with IPF (Fig. 1, Supplementary Fig. 4) and that conditional deletion of Nedd4-2 in lung epithelial cells of adult mice results in a spontaneous, chronic progressive, restrictive lung disease that shares clinical, radiological, and histopathological key features with IPF. This evidence concerns the gene NEDD4L and idiopathic pulmonary fibrosis.