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The leucine\u2010rich repeat containing RXFP1 and RXFP2 and the small peptide\u2010like RXFP3 and RXFP4 are the physiological targets for relaxin, insulin\u2010like (INSL) peptide 3, relaxin\u20103 and INSL5, respectively. RXFP1 and RXFP2 have at least two binding sites \u2013 a high\u2010affinity site in the leucine\u2010rich repeat region of the ectodomain and a lower\u2010affinity site in an exoloop of the transmembrane region. Although they respond to peptides that are structurally similar, RXFP3 and RXFP4 demonstrate distinct binding properties with relaxin\u20103 being the only peptide that can recognize these receptors in addition to RXFP1. Activation of RXFP1 or RXFP2 causes increased cAMP and the initial response for both receptors is the resultant of Gs\u2010mediated activation and G<jats:sub>oB<\/jats:sub>\u2010mediated inhibition of adenylate cyclase. With RXFP1, an additional delayed increase in cAMP involves \u03b2\u03b3 subunits released from G<jats:sub>i3<\/jats:sub>. In contrast, RXFP3 and RXFP4 inhibit adenylate cyclase and RXFP3 causes ERK1\/2 phosphorylation. Drugs acting at RXFP1 have potential for the treatment of diseases involving tissue fibrosis such as cardiac and renal failure, asthma and scleroderma and may also be useful to facilitate embryo implantation. Activators of RXFP2 may be useful to treat cryptorchidism and infertility and inhibitors have potential as contraceptives. Studies of the distribution and function of RXFP3 suggest that it is a potential target for anti\u2010anxiety and anti\u2010obesity drugs.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>150<\/jats:bold>, 677\u2013691. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707140\">10.1038\/sj.bjp.0707140<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0707140","type":"journal-article","created":{"date-parts":[[2007,2,12]],"date-time":"2007-02-12T11:14:43Z","timestamp":1171278883000},"page":"677-691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Relaxin Family Peptide Receptors \u2013 former orphans reunite with their parent ligands to activate multiple signalling pathways"],"prefix":"10.1111","volume":"150","author":[{"given":"M 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