<p>G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [<cite idref="PUB00004961"/>]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/). </p><p>The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7transmembrane (TM) helices [<cite idref="PUB00000131"/>, <cite idref="PUB00002477"/>, <cite idref="PUB00004960"/>].</p><p>The metastasis suppressor gene KiSS-1 encodes a number of RFamide-related peptides, the largest of which, metastin, contains 54 amino acids.An orphan G protein-coupled receptor, GPR54, has been identified as a receptor for these peptides [<cite idref="PUB00010559"/>]. GPR54 is highly expressed in placenta, pituitary, pancreas and spinal cord. Binding of KiSS-1-encoded peptidesto the receptor results in coupling to the Gq pathway, stimulating calciummobilisation, phosphatidylinositol hydrolysis, arachidonic acid release, ERK and p38 MAP kinase phosphorylation and stress fibre formation. It alsoinhibits cell proliferation. The distribution of GPR54, together with the finding that administration of KiSS-1 peptides in rat stimulates oxytocin secretion, suggests a role in regulation of endocrine function.</p> KiSS-1 peptide receptor