Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-? (proTGF?) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGF? activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGF?1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGF?1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGF?-binding protein for binding to proTGF?1. Association between GARP and proTGF?1 prevents the secretion of TGF?1. Integrin ?(V)?(6) and to a lesser extent ?(V)?(8) are able to activate TGF? from the GARP-proTGF?1 complex. Activation requires the RGD motif of latent TGF?, disulfide linkage between GARP and latent TGF?, and membrane association of GARP. Our results show that GARP is a latent TGF?-binding protein that functions in regulating the bioavailability and activation of TGF?.