TGF-beta 2 (transforming growth factor beta 2) is one of three closely related mammalian members of the large TGF-beta superfamily that share a characteristic cysteine knot structure. TGF-beta 1, -2 and -3 are highly pleiotropic cytokines proposed to act as cellular switches that regulate processes such as immune function, proliferation and epithelial-mesenchymal transition. Each TGF-beta isoform has some non-redundant functions; for TGF-beta 2, mice with targeted deletion show defects in development of cardiac, lung, craniofacial, limb, eye, ear and urogenital systems. Mouse TGF-beta 2 cDNA encodes a 414 amino acid (aa) precursor that contains a 19 aa signal peptide and a 395 aa proprotein. A furin-like convertase processes the proprotein to generate an N-terminal 283 aa latency-associated peptide (LAP) and a C-terminal 112 aa mature TGF- beta 2. Disulfide-linked homodimers of LAP and TGF-beta 2 remain non-covalently associated after secretion, forming the small latent TGF-beta 2 complex. Covalent linkage of LAP to one of three latent TGF-beta binding proteins (LTBPs) creates a large latent complex that may interact with the extracellular matrix. TGF-beta is activated from latency by pathways that include actions of the protease plasmin, matrix metalloproteases, thrombospondin 1 and a subset of integrins. Mature mouse TGF-beta 2 shares 100% aa identity with rat TGF-beta 2, and 97% aa identity with human, porcine, canine, equine and bovine TGF-beta 2. It demonstrates cross-species activity. In most cells, TGF-beta 2 signaling begins with binding to a complex of the accessory receptor betaglycan (also known as TGF-beta RIII) and a type II ser/thr kinase receptor termed TGF-beta RII, which then phosphorylates and activates another ser/thr kinase receptor, TGF-beta RI (also called activin receptor-like kinase (ALK) -5), or alternatively, ALK-1. The whole complex phosphorylates and activates Smad proteins that regulate transcription. In bone -related cells, however, TGF-beta 2 also signals through TGF-beta RIIB (a splice variant of TGF-beta RII), independently of TGF-beta RIII. Use of other signaling pathways that are Smad-independent allows for disparate actions observed in response to TGF-beta in different contexts.