Kisspeptin is a protein that acts like a switch to turn on the brain’s hormone system that controls puberty and reproduction. It boosts the release of hormones that tell the gonads to make sex hormones, and its levels rise during puberty. Mutations that stop kisspeptin or its receptor from working cause delayed or absent puberty, showing how essential it is.

The kisspeptin-GPR54 signaling complex is a key gatekeeper of human sexual maturation. Kisspeptins, encoded by the KISS1 gene, constitute a powerful stimulus for gonadotropin-releasing hormone-induced gonadotropin secretion. In addition, the KISS1 gene is a target for regulation by gonadal steroids in both sexes. The increase in hypothalamic kisspeptin expression at puberty is believed to contribute to maturation of the reproductive axis. Homozygous or compound heterozygous loss-of-function mutations in the GPR54 gene have been identified in familial and sporadic patients with isolated hypogonadotropic hypogonadism without olfactory abnormalities. In addition, mice with targeted deletions of Kiss1 or Gpr54 have a similar failure of sexual maturation. Study of these mutations provides an important contribution in the understanding of the role of the kisspeptin/GPR54 system in the control of human puberty development and reproductive function.