KISS1 encodes kisspeptin, a critical regulator of the hypothalamic-pituitary-gonadal (HPG) axis essential for puberty initiation and reproductive function 1. The protein functions as a ligand for the G-protein coupled receptor GPR54, triggering G(q) signaling and phospholipase C activation to stimulate gonadotropin-releasing hormone (GnRH) secretion 1. KISS1 neurons in the arcuate nucleus and anteroventral periventricular nucleus produce kisspeptin-54, which is cleaved into shorter bioactive peptides 1. Beyond reproduction, KISS1 neurons secrete CCN3, a brain-derived hormone that promotes bone anabolism, particularly during lactation when calcium demand is elevated 2. Kisspeptin expression is differentially regulated by sex steroids, enabling estrogen-mediated positive feedback during the ovulatory cycle 1. Metabolic factors, including leptin, tightly control KISS1 expression, linking energy balance to reproductive capacity 3. Loss-of-function mutations in KISS1 or GPR54 cause hypogonadotropic hypogonadism with absent puberty and low gonadotropin levels 1. KISS1 variants (rs12998 G>A and rs4889 C>G) are associated with idiopathic recurrent pregnancy loss 4. Mutations in the kisspeptin system also contribute to central precocious puberty 5, highlighting KISS1's role in determining pubertal timing.