Magnesium channel and transporter (Mg2+ transporter)

Magnesium channels and transporters are a diverse group of membrane proteins responsible for maintaining magnesium (Mg2+) homeostasis across cellular and organellar membranes [NIH, 2022]. As the second most abundant intracellular cation, magnesium is essential for over 300 enzymatic reactions, including ATP-dependent processes, DNA/RNA synthesis, and protein translation [StatPearls, 2023]. Key members of this group include the transient receptor potential melastatin 6 and 7 (TRPM6/7) chanzymes, which possess both ion channel and kinase domains, the solute carrier family 41 (SLC41) transporters, the magnesium transporter 1 (MagT1), and the mitochondrial RNA splicing 2 (MRS2) protein [MDPI, 2021; UniProt]. These proteins facilitate Mg2+ flux through various mechanisms, including passive diffusion down electrochemical gradients, active transport, and Na+/Mg2+ exchange [Wikipedia, 2024]. Dysregulation of these transporters is linked to various pathologies, including renal magnesium wasting, cardiovascular diseases, neurodegenerative disorders like Parkinson's, and several types of cancer where TRPM7 often promotes tumor progression [Nature Reviews Cardiology, 2017; PubMed, 2021]. Therapeutic strategies involve the use of magnesium supplements to restore levels or small-molecule inhibitors like TG100-115 and NS8593 to target specific channels in inflammatory and oncological contexts [MDPI, 2025; PubMed, 2022].

Other names

Magnesiotropic proteinMagnesium transport proteinMg2+ homeostasis regulatorTransient receptor potential melastatin 7 (TRPM7)Transient receptor potential melastatin 6 (TRPM6)Magnesium transporter 1 (MagT1)Solute carrier family 41 member 1 (SLC41A1)Mitochondrial RNA splicing 2 protein (MRS2)Cyclin and CBS domain divalent metal cation transport mediator (CNNM)

Direct inhibition of ion-conducting pores, inhibition of C-terminal alpha-kinase activity, competitive substrate supplementation, and modulation of Na+/Mg2+ exchange stoichiometry.