Loss of function of GPR54 was reported as a cause of isolated hypogonadotropic hypogonadism 7, 8, and since then, a large amount of evidence has supported that Kp–GPR54 is the essential gatekeeper of gonadotropin‐releasing hormone (GnRH) neurons, which have a central role in puberty onset and reproduction 9, 10, 11, 12. This evidence concerns the gene KISS1R and hypogonadotropic hypogonadism.