Notably, Meng et al. reported that specific deletion of Smad4 from renal tubular epithelial cells ameliorates UUO-induced renal fibrosis by suppressing Smad3 responsive promoter activity and decreasing the binding of Smad3 to its target genes independent of its phosphorylation and nuclear translocation [37]. The gene discussed is SMAD4; the disease is renal fibrosis.