We Have recently demonstrated that the human solute carrier, SLC41A1, is a Mg2+ transporter that is regulated by extracellular magnesium. A BLAST search found a closely related protein encoded by SLC41A2 that may have related functional properties. In order to determine the function of SLC41A2, the corresponding cRNA was expressed in Xenopus laevis oocytes and Mg2+ currents were determined under voltage-clamp conditions. Further, real-time RT-PCR was performed to determine if SLC41A2 expression is regulated by magnesium. When expressed in oocytes, SLC41A2 mediates voltage-dependent and saturable Mg2+ uptake with a Michaelis constant of 0.34 +/- 0.05 mM. Expressed SLC41A2 transports a range of other divalent cations: Ba2+, Ni2+, Co2+, Fe2+, or Mn2+, but not Ca2+, Zn2+, or Cu2+. Mg2+ transport was inhibited by large concentrations of Ca2+. Real-time reverse transcription polymerase chain reaction of RNA isolated from renal distal tubule epithelial (MDCT) cells cultured in low-magnesium media relative to normal media and in kidney cortex of mice maintained on low-magnesium diets compared to those animals consuming normal diets showed that SLC41A2 transcript, unlike SLC41A1 mRNA, is not responsive to magnesium. These studies suggest that SLC41A2 is a Mg2+ transporter that might be involved in magnesium homeostasis in epithelial cells. (c) 2005 Elsevier Inc. All rights reserved.