Nedd4-2 is an E3 ubiquitin protein ligase involved in posttranscriptional regulation by ubiquitination and targeting for proteasomal degradation of proteins implicated in the pathogenesis of lung disease, including surfactant protein C (Sftpc), the epithelial sodium channel ENaC, and Smad2/3, the intracellular mediators of transforming growth factor β (TGFβ) signaling (17, 20–23). This evidence concerns the gene SFTPC and lung disorder.