TGFβ is synthesized as homodimeric precursor containing a pro-peptide sequence LAP, (1), and then processed by furin. LAP remains associated with the mature TGFβ by non-covalent interactions in a small latent complex (2), which in turn is linked by disulfide bonds to one of the latent TGFβ binding proteins (LTBP1–4) (3). TGFβ is secreted as part of this large latent TGFβ complex (LLC) (3), and it is incorporated as component of the extracellular matrix (ECM), which acts as a reservoir of the cytokine (4). TGFβ must undergo a highly regulated activation process by which mature cytokine is released (5) to enable binding to its receptor complex (TβRI and TβRII) (6) and signal through Smad2/Smad3 pathway (7). Known TGFβ activators are listed in the upper left.