GnRHR, the gonadotropin-releasing hormone receptor, belongs to the G protein-coupled receptor family. It is a crucial regulator in the hypothalamic-pituitary-gonadal (HPG) axis, which controls human sexual and reproductive development. When its ligand GnRH binds, it activates complex signaling pathways. In pituitary gonadotrope cells, it triggers G protein subunit dissociation, leading to the production and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), along with phospholipase C, inositol phosphate production, and protein kinase C activation [1].

Mutations in GNRHR are linked to normosmic hypogonadotropic hypogonadism. Homozygous and compound heterozygous mutations in the GNRHR gene are frequent genetic causes of this disorder, resulting in various clinical symptoms such as delayed puberty, infertility, and impaired sexual development. These mutations can have different inheritance modes [3]. In some cases, patients with GNRHR-associated hypogonadism can experience spontaneous recovery of the HPG axis [2].

In conclusion, GnRHR is essential for the normal function of the HPG axis and human reproduction. Studies on GNRHR-related mutations in patients have provided insights into the role of GnRHR in hypogonadotropic hypogonadism. Understanding GnRHR's genomic and protein structure and the impact of its mutations is crucial for diagnosing and potentially treating related reproductive disorders.