Human KISS1 Receptor (KISS1R) Protein

Background

KISS1R, also known as GPR54, is a G protein-coupled receptor activated by kisspeptins, a family of peptide ligands derived from the KISS1 gene. KISS1R plays a crucial role in regulating the hypothalamic-pituitary-gonadal (HPG) axis, particularly in puberty onset and reproductive function. It is highly expressed in the hypothalamus, where kisspeptin signaling stimulates the secretion of gonadotropin-releasing hormone (GnRH), which in turn regulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. This pathway is essential for normal sexual maturation, fertility, and reproductive hormone balance. Mutations in KISS1R are associated with hypogonadotropic hypogonadism, delayed puberty, and infertility. Beyond reproduction, KISS1R signaling is implicated in metastasis suppression, as kisspeptins inhibit cell migration and invasion in cancers such as melanoma and breast cancer. Dysregulation of KISS1R has also been linked to metabolic disorders and polycystic ovary syndrome (PCOS). Therapeutically, KISS1R agonists and antagonists are being explored for treating infertility, hormone-driven cancers, and reproductive disorders.