Thromboxane A
2 (TXA
2), an unstable arachidonic acid metabolite, elicits diverse physiological/pathophysiological actions, including platelet aggregation and smooth muscle contraction. TXA
2 has been shown to be involved in allergies, modulation of acquired immunity, atherogenesis, neovascularization, and metastasis of cancer cells. The TXA
2 receptor (TP) communicates mainly with G
q and G
13, resulting in phospholipase C activation and RhoGEF activation, respectively. In addition, TP couples with G
11, G
12, G
13, G
14, G
15, G
16, G
i, G
s and G
h. TP is widely distributed in the body, and is expressed at high levels in thymus and spleen. The second extracellular loop of TP is an important ligand-binding site, and Asp
193 is a key amino acid. There are two alternatively spliced isoforms of TP, TP
and TP
b2;, which differ only in their C-terminals. TP
and TP
b2; communicate with different G proteins, and undergo hetero-dimerization, resulting in changes in intracellular traffic and receptor protein conformations. TP cross-talks with receptor tyrosine kinases, such as EGF receptor, to induce cell proliferation and differentiation. TP is glycosylated in the N-terminal region for recruitment to plasma membranes. Furthermore, TP conformation is changed by coupling to G proteins, showing several states of agonist binding. Finally, several drugs modify TP-mediated events; these include cyclooxygenase inhibitors, TXA
2 synthase inhibitors and TP antagonists. Some flavonoids of natural origin also have TP receptor antagonistic activity. Recent advances in TP research have clarified TXA
2-mediated events in detail, and further study will supply more beneficial information about TXA
2 pathophysiology.