Taken together, these studies (i) demonstrate that pirfenidone slowed progression of pulmonary fibrosis in conditional Nedd4-2−/− mice at least in part by suppression of elevated TGFβ signaling; (ii) indicate that therapeutic benefits of pirfenidone are at least in part related to its effects on AT2 cells; and (iii) support the usefulness of this model for preclinical testing of novel anti-fibrotic compounds. The gene discussed is NEDD4L; the disease is pulmonary fibrosis.