XMEN disease. (A) XMEN disease clinical features. Major features are present in almost all XMEN patients, while minor features are found only in some patients. (B) Model of the role of MAGT1 in TCR activation. In normal T cells, stimulation of the TCR triggers a Mg²⁺ flux through MAGT1. This transient increase of intracellular Mg²⁺ is required for the activation of phospholipase C γ1 (PLCγ1) required for the downstream generation of Ca²⁺ flux through ORAI by promoting the release of Ca²⁺ from the endoplasmic reticulum via inositol 1,4,5-triphosphate (IP₃) and its receptor. (C) Model of role of MAGT1 in Mg²⁺ homeostasis and NKG2D expression. In XMEN patients, the absence of MAGT1 leads to the chronic reduction of intracellular free Mg²⁺, which is required to maintain the expression of NKG2D.