The P2Y receptors are a widely expressed group of G-protein coupled receptors (GPCRs). P2Y receptors are activated by nucleotides which are extracellular signaling molecules that are released from damaged cells or secreted via non-lytic mechanisms during inflammation, ischemia or hypoxia.

P2Y12 receptor, like all P2Y receptors, is a 7-membrane spanning protein coupled to a G protein. Most of the seven transmembrane helices of P2YR12 are not perpendicular to the plane of the membrane but are tilted or kinked. The carboxy-terminal helix VIII is parallel to the membrane lipid bilayer. The receptor contains 342 amino acid residues and two potential N-linked glycosylation sites at its extra-cellular amino terminus, which may modulate its activity.

ADP and some of its analogues stimulate P2YR12-mediated inhibition of adenylyl cyclase through activation of the G_αi2 G protein subtype, although effective coupling may also occur to G_αi1 G and G_αi3 G.

P2YR12 is an important cofactor of platelet aggregation and secretion induced by several agonists including collagen, TXA2, thrombin and specific antibodies cross-linking FcγRIIa receptors. It also plays an important role in shear-induced platelet aggregation and in platelet thrombus formation and stabilization on collagen-coated surfaces or ruptured atherosclerotic plaques under flow conditions.

Inherited abnormalities of P2YR12 include an autosomal recessive disorder causing severe receptor deficiency. Due to this abnormality, ADP, even at very high concentrations, does not induce full and irreversible platelet aggregation, nor does it inhibit the stimulation of platelet adenylyl cyclase causing excessive bleeding and additional coagulative dysfunction.