TACR2 (tachykinin receptor 2) is a G protein-coupled receptor located on chromosome 10.3 that serves as the primary receptor for the neuropeptide substance K (neurokinin A), with secondary binding to substance P and neurokinin B 12. Upon ligand binding, TACR2 activates dual signaling pathways: phospholipase C-mediated inositol phosphate hydrolysis via Gq protein coupling and adenylate cyclase activation leading to increased cAMP levels 34. TACR2 demonstrates the highest mRNA expression among tachykinin receptors in human lower esophageal sphincter smooth muscle, suggesting a prominent role in regulating esophageal function 5. The receptor is widely distributed in the brain and has been functionally implicated in stress-induced hippocampal acetylcholine release 6. Clinically relevant dysregulation occurs in female infertility conditions including polycystic ovarian syndrome, advanced maternal age, and endometriosis, where altered TACR2 expression in granulosa cells correlates with reduced fertility 7. TACR2 represents a prognostic biomarker in gastric cancer, with elevated expression associated with worse overall survival in integrated risk models 8. TACR2 polymorphisms (Ile23Thr and Arg375His) are prevalent in human populations but do not functionally impair agonist or antagonist responses 9. Recent discovery of selective TACR2 antagonists like tumonolide offers therapeutic potential for modulating pathways implicated in pulmonary fibrosis and metabolic disorders 10.