GNRH1 encodes gonadotropin-releasing hormone 1, a hypothalamic neuropeptide that serves as a master regulator of mammalian reproduction 1. Synthesized by GnRH neurons that originate in the olfactory placode during early embryogenesis and migrate to the hypothalamus 2, GNRH1 is released in synchronized pulses into the hypothalamic-pituitary portal system where it binds GnRH type 1 receptors on anterior pituitary gonadotrophs 1. This binding stimulates synthesis and secretion of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which subsequently stimulate gonadal sex steroid production and gametogenesis 3. Biallelic GNRH1 mutations cause congenital hypogonadotropic hypogonadism (CHH), characterized by deficient pubertal development, low gonadotropin levels, and isolated reproductive dysfunction without olfactory or pituitary abnormalities 4. Frameshift, splice-site, and missense mutations all produce severe reproductive phenotypes 4, though monoallelic variants show variable pathogenicity 5. Heterozygous mutations may produce mild forms of GnRH deficiency, occasionally in combination with other gene mutations 5. Beyond monogenic disease, aberrant GnRH neuron hyperactivity contributes to polycystic ovary syndrome pathogenesis, promoting hyperandrogenism and anovulation 6. These findings validate GNRH1's pivotal role in human reproductive development and fertility, with therapeutic implications including gonadotropin replacement and GnRH receptor modulation 4.