KISS1R is a G protein-coupled receptor that serves as the central regulator of reproductive function by binding kisspeptins to control the hypothalamic-pituitary-gonadal (HPG) axis 1. Upon kisspeptin binding, KISS1R activates Gq-dependent signaling via phospholipase C, increasing intracellular calcium and depolarizing GnRH neurons to stimulate gonadotropin-releasing hormone secretion 1. The receptor also engages β-arrestin-dependent MAPK signaling and recruits phosphatase DUSP18 for additional regulatory functions 2. KISS1R mutations cause reproductive disorders: loss-of-function variants cause congenital hypogonadotropic hypogonadism (CHH) characterized by absent puberty and gonadotropic deficiency 3, while gain-of-function mutations trigger central precocious puberty 4. Beyond reproduction, KISS1R regulates peripheral processes including endometrial homeostasis and trophoblast invasion 5, and coordinates sex hormone production through the kisspeptin-KISS1R-AKT-SHBG axis 6. Environmental compounds like musk ambrette can activate KISS1R to trigger early puberty 7. Clinically, KISS1R antagonists represent potential therapeutics for precocious puberty, endometriosis, and hormone-dependent cancers 8.