TGFβ signaling plays a central role in SSc pathogenesis and is evidenced by an increased expression of pSmad1 in SSc skin and cultured fibroblasts (26), elevated phosphorylated Smad2/3 levels and increased nuclear localization of phosphorylated Smad2/3 in these cells (27). The gene discussed is TGFB1; the disease is systemic sclerosis.