These studies reveal that deletion of the Smad3 gene protects against renal tubulointerstitial fibrosis (TIF) and mesangial matrix expansion, but the impact of Smad3 on other characteristics of renal fibrosis such as glomerular basement membrane (GBM) thickening, atrophy, and albuminuria cannot be uniformly confirmed. The gene discussed is SMAD3; the disease is renal fibrosis.