The Gene That Was Named Twice

Kisspeptin has one of the strangest origin stories in endocrinology. The KISS1 gene was first identified as a metastasis suppressor in melanoma (hence 'kiss' — Kiss of Death for metastasis). Only later was it discovered that its encoded peptide is the upstream gatekeeper of the entire reproductive axis, acting on GnRH neurons to permit puberty.

The proof came from genetics: people and mice with loss-of-function mutations in the kisspeptin receptor (KISS1R/GPR54) don't go through puberty at all. That established kisspeptin signaling as the gate that must open for reproductive function to begin. Kisspeptin-10 is the shortest fragment that fully activates the receptor — a useful research handle on a pathway that sits above even GnRH.