Spexin (SPX), a novel peptide coevolved with the galanin/kisspeptin family, was first identified by bioinformatics prior to its protein purification/functional studies. Its mature peptide is highly conserved among different vertebrate classes. Based on the studies in mammals and fish models, SPX was found to be widely distributed at tissue level, secreted into systemic circulation, identified at notable levels in central nervous system and peripheral tissues, and has been confirmed/implicated in multiple functions in different tissues/organs, suggesting that SPX may serve as a neuroendocrine signal with pleotropic functions. In this article, different isoforms of SPX and their binding with their cognate receptors GalR2 and GalR3, the biological functions of SPX reported in mammals including GI tract movement, energy balance and weight loss, fatty acid uptake, glucose homeostasis, nociception and cardiovascular/renal functions, as well as the recent findings in fish models regarding the role of SPX in reproduction and feeding control will be reviewed with interesting questions for future investigations.
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