Smad anchor for receptor activation (SARA) is known as Smad cofactor that interacts directly with Smad2/3 and functions to recruit Smad2/3 to the TGF-beta receptor. SARA plays an essential role in TGF-beta-induced Smad2 activation and it may modulate TGF-beta signaling through regulating the balance between Smad2 and Smad3. SARA also functions as an anchor for catalytic subunit of protein phosphatase 1 (PP1c) and maybe involved in the dephosphorylation of TGF-beta type I receptor (TbetaR-I) mediated by Smad7. The expression of SARA changes as the development of epithelial to mesenchymal transition (EMT) and fibrosis and it plays a critical role in the maintenance of epithelial cell phenotype. Modulation of SARA may provide a new therapeutic approach to TGF-beta-mediated EMT and fibrosis.