Transmembrane thiol isomerase TMX1 counterbalances the effect of ERp46 to inhibit platelet activation and integrin αIIbβ3 function.

TMX1 not only oxidizes integrin αIIbβ3 disulfides that are reduced by ERp46 but also directly oxidizes ERp46 to suppress its reduction of integrin αIIbβ3. Thus, TMX1 is critical for maintaining platelets in a quiescent state and counterbalancing the effect of ERp46 to prevent platelet overactivation.