The importance of the kisspeptin–GPR54 system in reproductive function came to light in 2003 when it was discovered that some human families displaying hypogonadotropic hypogonadism and absence or delay in puberty bore mutations in the GPR54 gene (de Roux et al., 2003; Seminara et al., 2003). Here, KISS1 is linked to hypogonadotropic hypogonadism.