G protein-coupled receptors(GPCRs)are the largest group of the cell membrane receptors playing critical biological functions.Human genome encodes approximately 400 non-olfactory GPCRs that are thought to have endogenous ligands.So far,the endogenous ligands of approximately 120 GPCRs are remained unknown and these receptors are termed as orphan GPCRs.Protein/peptide hormones can activate about 50%of GPCRs with known endogenous ligands,being the most important group of the endogenous GPCR ligands.Thus,we deduced that secretory proteins and peptides are important candidates of orphan GPCR ligands.