TGF-beta 1 is one member of a six gene family that has been described in mammals, birds, fish and frog. The name TGF-beta is applied to a 24-28 kDa disulfide-linked dimer that is generated through the proteolytic processing of a larger precursor molecule. For TGF-beta 1, a 50-55 kDa, 391 amino acid (aa) proprecursor is first, covalently linked to a second proprecursor (creating a disulfide-linked homodimer), and second, internally cleaved to generate two covalently-linked homodimers that remain non-covalently associated. The smallest homodimer representing aa 279-390 of the proform is TGF-beta 1; the largest homodimer representing aa 30-278 of the proform is termed LAP (Latency-associated Peptide). The LAP homodimer wraps itself around the smaller TGF-beta 1 homodimer, thus blocking an interaction of mature TGF-beta with its receptors. Almost all cells secrete the inactive TGF-beta :LAP complex, and most do so with LAP covalently bound to a very large 120-160 kDa LTBP (Latent TGF-beta Binding Protein), platelets being a notable exception. LTBP associates with multiple matrix components and this serves to store TGF-beta extracellularly in a non-active form. When TGF-beta signaling is needed, the LTBP:matrix association is disrupted, and the TGF-beta :LAP complex is exposed to multiple LAP binding partners such as TSP-1 and various Integrins. Interactions with these factors cause LAP to unwrap and dissociate from TGF-beta, resulting in TGF-beta "activation" and receptor binding. Ther are three human TGF-beta 1 LAPs and TGF-beta 1 LAP shares 36% and 33% aa sequence indentity with TGF-beta 2 LAP and TGF-beta 3 LAP, respectively. Human to mouse, TGF-beta 1 LAP shares 86% aa sequence identity.