SMAD2 and Restrictive ventilatory defect: Besides the important similarities of pulmonary phenotypes caused by the congenital vs. the conditional deletion of Nedd4-2 in the murine lung, including restrictive lung disease with patchy fibrotic remodeling of distal airspaces due to dysregulated Smad2/3 signaling, leading to increased levels of TGFβ, remodeling of distal airways with goblet cell metaplasia and increased expression of Muc5b, as well as high pulmonary mortality (Figure 1, Figure 2 and Figure 5) [9,29], our study also revealed some striking age-dependent differences.