MagT1, or magnesium transporter 1, is a subunit of the oligosaccharide protein complex with thiol-disulfide oxidoreductase activity, crucial for the N-glycosylation process [1]. It is also significantly involved in magnesium homeostasis, with magnesium being essential for over 600 enzymatic reactions in the human body [3].

In MagT1-deficient mice (Magt1-/y), accelerated occlusive arterial thrombus formation, a shortened bleeding time, and profound brain damage upon focal cerebral ischemia were observed. These defects were due to increased calcium influx, enhanced second wave mediator release, and hyperphosphorylation of key proteins in the platelet activation pathway. Supplementation of MgCl2 or blockade of TRPC6 channel normalized platelet aggregation responses. Haploinsufficiency of TRPC6 in Magt1-/y mice could also normalize GPVI signaling, platelet aggregation, and thrombus formation in vivo, suggesting a functional link between MagT1 and TRPC6 [1]. In XMEN disease patients with MagT1 deficiency, severe platelet dysfunction and impaired platelet glycoprotein N-glycosylation were found, with abnormal platelet shapes, impaired aggregation, and integrin activation, which were corrected after hematopoietic stem cell transplantation [2].

In conclusion, MagT1 is essential for N-glycosylation and magnesium homeostasis. Studies using MagT1-deficient mouse models have revealed its crucial role in platelet function and arterial thrombosis-related processes. Understanding MagT1's functions provides insights into the pathogenesis of diseases such as XMEN disease and potential risks of arterial thrombosis and stroke [1,2].