TRHR (thyrotropin-releasing hormone receptor) is a G-protein-coupled receptor located on chromosome 8 that mediates TRH signaling through activation of the phosphatidylinositol (IP3)-calcium-protein kinase C (PKC) pathway 1. Beyond its classical role in thyroid hormone regulation, TRHR significantly influences lean body mass (LBM) and muscle metabolism. Genome-wide association studies identified TRHR polymorphisms (rs16892496 and rs7832552) associated with LBM variation, with carriers of unfavorable genotypes showing 2.5-2.7 kg lower LBM 2. The rs16892496 variant also correlates with reduced appendicular fat-free mass and muscle strength in older women 3. Clinically, TRHR mutations cause central congenital hypothyroidism (CCH), an underdiagnosed disorder characterized by deficient TSH production 4. A documented missense mutation (I131T) impairs TRH binding affinity and Gq protein coupling, causing moderate hypothyroidism in homozygotes and hyperthyrotropinemia in heterozygotes 5. TRHR mutations account for a subset of CCH cases 6, with an estimated carrier frequency of 0.059% in the general population 7. Additionally, aberrant TRHR expression occurs in pituitary somatotroph tumors, contributing to endocrine tumorigenesis 8.