TACR2 (NK2R) is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P. TACR2 functions in GI motility, visceral sensitivity and secretion, and loss of TACR2 has been shown to lead to gastric emptying disturbance. TACR2 is implicated in the mediation of smooth muscle contraction in central airways and the development of asthma. Additionally, TACR2 is believed to play a role in neurological disorders, and antagonists of TACR2 are currently in clinical trials as potential therapies for major depressive disorder. In immunohistochemistry, TACR2 has highest membranous positivity in the gastrointestinal tract, and is also found in the urinary bladder, prostate, reproductive tissues, epithelial cells in the breast, ovary, eccrine glands, stomach and testis, and in smooth muscle in various tissues. References: Neurogastroenterol Motil. 2017 Nov;29(11), PMID: 28585346; CNS Neurol Disord Drug Targets. 2010 Nov;9(5):627-35, PMID: 20632965