Although both Smad 3 and Smad 2 act downstream of TGFβ, unexpectedly, specific deletion of Smad 2 in kidney significantly enhanced Smad 3 activity, collagen matrix expansion and fibrosis, indicating that Smad 2 functions as a negative regulator of TGFβ-driven renal fibrosis [17]. The gene discussed is TGFB1; the disease is renal fibrosis.