Prolactin-releasing peptide (PrRP) a bioactive peptide, was originally identified as an endogenous ligand of the orphan human G-protein coupled receptor, seven transmembrane domain receptor, GPR10 (hGR3, also called PrRP receptor). Like the majority of orphan receptors, PrRP receptor shows a low level of sequence homology with known GPCRs. Notwithstanding, a certain degree of homology has been reported to members of the neuropeptide Y (NPY) family of receptors. Neuropeptide Y is a 36- residue C-terminally amidated polypeptide hormone and neurotransmitter with the presence of an α-helix involving the 20 C-terminal residues, whereas the N-terminus part seems more flexible and is influenced by the medium environment. It has been recently demonstrated that the PrRP receptor may modulate neurotransmission specifically at glutamatergic synapses through the interaction with the same PDZ domain proteins that interact with AMPA receptors.