Platelet glycoprotein VI (GPVI) (GPVI)

Platelet glycoprotein VI (GPVI) is the primary signaling receptor for collagen on platelets and the central initiator of the GPVI signaling cascade. Upon vascular injury, GPVI binds to exposed subendothelial collagen, triggering a signaling pathway mediated by the Fc receptor gamma-chain (FcRγ), Syk kinase, and PLCγ2, which results in platelet activation, secretion, and thrombus formation (14, 15, 18). GPVI is a unique antiplatelet target because it is essential for pathological thrombosis but plays a minimal role in physiological hemostasis, offering a therapeutic window with a significantly lower risk of major bleeding compared to traditional agents like aspirin or P2Y12 inhibitors (14, 17, 20). Current drug candidates include glenzocimab, a humanized Fab fragment that blocks the receptor directly, and revacept, a soluble GPVI-Fc fusion protein that acts as a decoy for collagen (1, 3, 11). Beyond its role in cardiovascular diseases like stroke and myocardial infarction, the GPVI signaling cascade is increasingly recognized for its involvement in thrombo-inflammation, cancer metastasis, and viral-induced coagulopathy, such as that seen in COVID-19 (13, 25, 28).

Other names

GP6Glycoprotein 6Platelet-specific collagen receptorCollagen receptor glycoprotein VIGPVI signaling pathway

Inhibition of collagen and fibrin(ogen) binding to the GPVI receptor or inhibition of downstream signaling components (e.g., Syk kinase), thereby blocking the activation cascade that leads to platelet aggregation and thrombus growth.