TGF-beta 1 is expressed as a proprotein that is cleaved within the trans-Golgi to yield a latency-associated peptide (LAP) and the mature TGF-beta 1. Disulfide-linked homodimers of LAP and TGF-beta 1 remain noncovalently associated after secretion, forming the small latent TGF-beta 1 complex. Purified LAP can also associate with active TGF-beta and neutralize TGF-beta activity. Covalent linkage of LAP to one of three latent TGF-beta binding proteins (LTBPs) creates a large latent complex that can interact with the extracellular matrix. TGF-beta activation from latency is controlled by multiple factors including Plasmin, MMP-9, Thrombospondin-1, and various Integrins. The TGF-beta 1 LAP is capable of complexing with and inactivating all other human TGF-beta isoforms and those of most other species.