Consistent with the finding that the endogenous ratio of Smad2 and Smad3 may ultimately influence the cytostatic function of Smad3 (Kim et al., 2005), results from our recent study demonstrated that conditional knockout of Smad2 from tubular epithelial cells enhances Smad3-mediated renal fibrosis in vivo and in vitro, which is associated with the increase in phosphorylation and nuclear translocation of Smad3, promotion of the Smad3 responsive promoter activity, and binding of Smad3 to Col1A2 promoter (Meng et al., 2010). The gene discussed is SMAD3; the disease is renal fibrosis.