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This review aims to provide an overview of the function of Mg<jats:sup>2+<\/jats:sup>in human health and disease. In short, Mg<jats:sup>2+<\/jats:sup>plays an important physiological role particularly in the brain, heart, and skeletal muscles. Moreover, Mg<jats:sup>2+<\/jats:sup>supplementation has been shown to be beneficial in treatment of, among others, preeclampsia, migraine, depression, coronary artery disease, and asthma. Over the last decade, several hereditary forms of hypomagnesemia have been deciphered, including mutations in transient receptor potential melastatin type 6 (TRPM6), claudin 16, and cyclin M2 (CNNM2). Recently, mutations in Mg<jats:sup>2+<\/jats:sup>transporter 1 (MagT1) were linked to T-cell deficiency underlining the important role of Mg<jats:sup>2+<\/jats:sup>in cell viability. 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