GNRH2 (gonadotropin-releasing hormone 2) is a highly conserved peptide hormone that has diverged functionally from its paralog GnRH1 in mammals 1. Unlike GnRH1, which drives reproduction through gonadotropin regulation, GNRH2 is ubiquitously expressed in peripheral tissues and brain regions outside the hypothalamic-pituitary axis, suggesting distinct biological roles 1. GNRH2 coordinates nutritional status with sexual behavior in the female brain and directly stimulates steroidogenesis in reproductive organs, particularly the testis 1. The gene shows conservation across 500 million years of evolution, indicating critical selective pressure, though it is absent or non-functional in some mammalian species including rodents 1. GNRH2 expression occurs in gastrointestinal enteric neurons where it influences motility and secretion 2. Clinically, GNRH2 and its receptor represent emerging therapeutic targets; GNRH2 analogues demonstrate anti-proliferative and pro-apoptotic effects against reproductive cancers including breast, ovarian, endometrial, and prostate malignancies 3. Genetic variants in GNRH2 associate with osteosarcoma susceptibility and survival outcomes 4, and GNRH2 shows protective associations with esophageal cancer risk 5.