In ADPKD nuclear accumulation of SMAD2/3 in cystic epithelial cells and in interstitial fibroblasts, as well as elevated expression of target genes, points to a role of SMAD2/3-regulated signaling in epithelial dedifferentiation and fibrosis [24, 27, 65]. The gene discussed is SMAD2; the disease is autosomal dominant polycystic kidney disease.