Kisspeptin and its receptor GPR56 are now known to be essential switches that turn on the reproductive hormone system, helping start puberty and control fertility. Recent work also shows they link metabolism to reproduction and may affect ovulation timing, but the paper is a broad review rather than a new treatment guide.

Identification, in late 2003, of inactivating mutations of the G protein-coupled receptor GPR54 as causative factor for absence of puberty and hypogonadotropic hypogonadism in humans and mice was a major breakthrough in modern Neuroendocrinology, and drew considerable interest on the characterization of the roles of this receptor and its ligands (kisspeptins, encoded by the KiSS-1 gene) in the physiological control of essential facets of reproduction. After 3 years of intense research activity, kisspeptins are universally recognized as essential activators of the gonadotropic axis, with key roles in puberty onset and the control of gonadotropin secretion. While these fundamental functions are now well settled, novel aspects of kisspeptin/GPR54 physiology have emerged, including their involvement in the neuroendocrine control of ovulation and the metabolic gating of reproductive function. In addition, the 'comparative endocrinology' of this system has begun to be explored recently. These facets of kisspeptin/GPR54 function, as fundamental gatekeepers of reproduction, will be comprehensively reviewed herein.