Magnesium is one of the most abundant cation in the cell. It is crucial for the proper functioning of various tissues such as the brain, muscle, bone and the nervous system. Currently there are only two types of Mg²⁺ transport systems which have had their complete structures discovered. MgtE and CorA are the prokaryotic homologues of the SLC41 and MRS2 magnesium transporters.

In eukaryotes, MRS2 protein is expressed in mitochondrial inner membranes. MRS2 is required for normal mitochondrial magnesium homeostasis and for proper myelination in the central nervous system. Notably, the expression of MRS2 serves as a genetic hallmark for embryonic stem cells².

MRS2 is comprised of two adjacent transmembrane domains. The first domain ends with a gly-met-asn motif and additional secondary structures. A long N-terminal and a short C-terminal sequence are located in the inner side of the mitochondrial membrane leaving the short loop connecting the transmembrane domains protruding to its exterior.

In addition to its Mg²⁺ permeability, MRS2 transporters somewhat transport Ni²⁺. However, they are not permeable to Ca²⁺, Mn²⁺ and Co²⁺. MRS2 transporters can be blocked by Cobalt(III)-hexaamine, an analog of the hydrated Mg²⁺ ion and their activity is regulated by matrix Mg²⁺ concentrations. Increase in Mg²⁺ concentration causes a shift of the current-voltage relationship to a more negative potential as expected from the reduction in driving force and significantly reduces the channels’ open-time probability².

Several SNPs in the MRS2 gene are associated an increased risk of developing type 2 diabetes in women of African American and Hispanic American origin³.