Recent findings indicate that the aberrant ECM synthesis by cultured SSc fibroblasts is due, at least in part, to the constitutively enhanced activation of the TGFβ signaling, which may result from the elevated levels of TGFβ receptor type I, inappropriate overexpression/activation of Smad2 and Smad3, and/or decreased Smad7 expression. The gene discussed is SMAD2; the disease is systemic sclerosis.