Later, hypogonadotropic hypogonadism was also observed in Kiss1 knockout mice (12), while precocious puberty onset occurred in humans with either gpr54-activating mutation leading to prolonged in vitro activation of intracellular signaling pathways in response to kisspeptin (13) or Kiss1 mutations leading to higher in vitro kisspeptin resistance to degradation (14). The gene discussed is KISS1R; the disease is hypogonadotropic hypogonadism.