TACR1 encodes the neurokinin 1 receptor (NK1R), a G protein-coupled receptor that binds substance P with the highest affinity among tachykinin ligands, followed by neurokinin A and neurokinin B. Ligand binding activates phospholipase C-mediated phosphatidylinositol hydrolysis and adenylate cyclase signaling, increasing intracellular calcium and cAMP. Beyond canonical nociception and itch modulation, TACR1 has emerged as a key node in multiple disease pathways. Genetic variants in TACR1 associate with bipolar disorder, attention-deficit hyperactivity disorder, and alcohol dependence syndrome 1, while association studies show nominal evidence in panic disorder 2. Recent evidence reveals that substance P signaling through TACR1 exacerbates periodontitis during sleep deficiency by promoting vascular permeability and immune infiltration 3, and drives breast cancer metastasis through an extracellular RNA-TLR7 axis 4. TACR1 also mediates pain-induced itch suppression via brainstem circuits 5. Clinically, TACR1 polymorphisms predict response to NK1 receptor antagonist-based antiemetic regimens in chemotherapy-induced nausea and vomiting 6, with aprepitant and related antagonists approved for this indication. TACR1 variation also influences postoperative nausea severity in a sex-dependent manner 7 and sensitivity to NK1R antagonists in alcohol preference 8.