The present invention is directed to compositions and methods related tosoluble G-protein coupled receptors (sGPCR). In ceratin aspects the inventionincludes compositions and methods related to a soluble corticotropin releasingfactor receptor related protein, sCRFR2, as well as its effects on CRFRsignaling and interaction between CRF family ligand and CRFR receptors,including but not limited to CRFR2, CRFRl and functional or signaling capablevariants thereof.