MTNR1B encodes melatonin receptor 1B, a G protein-coupled receptor mediating melatonin's reproductive and circadian actions through pertussis toxin-sensitive G proteins that inhibit adenylate cyclase activity. The receptor regulates glucose homeostasis and insulin secretion, functioning as a high-affinity melatonin binding protein at the plasma membrane. Genetically, multiple MTNR1B polymorphisms associate with metabolic disease risk. The rs1387153 variant significantly increases gestational diabetes mellitus (GDM) susceptibility across diverse populations 1, with similar associations for rs10830962, rs4753426, and rs10830963 variants 2. The rs10830963 G allele correlates with impaired early-phase insulin secretion and elevated fasting glucose even in healthy individuals, suggesting primary effects on beta cell function 3. GDM-associated variants show independent risk prediction, modified by gene-gene and gene-environmental interactions including pre-pregnancy BMI and protein intake 24. Regarding non-metabolic conditions, MTNR1B rs4753426 and rs10830963 polymorphisms show no significant association with adolescent idiopathic scoliosis (AIS) risk overall, though Asian subgroup analyses revealed associations with rs4753426 56. Clinically, MTNR1B genetic variants serve as biomarkers for GDM and type 2 diabetes susceptibility, though mechanistic understanding of how melatonin signaling disruption impairs glucose regulation remains incomplete 7.