DMT1 (Nramp2/DCT1) is the major apical iron transporter in absorptive cells of the duodenum, but also transports transferrin-iron across the membrane of acidified endosomes in peripheral tissues. DMT1 mRNA and protein expression has been detected in rat and mouse kidney, but its role at that site remains to be clarified.Immunoblotting and immunohistochemistry with specific affinity purified anti-DMT1 polyclonal antibodies were used to study expression and localization of DMT1 in mouse kidney. Possible regulation of DMT1 protein expression by the body iron stores also was examined in normal mice deprived of dietary iron, and in the genetically anemic mk mice that bear a loss of function mutation at DMT1 (G185R).In microsomal kidney fractions, DMT1 isoform I (encoded by the iron responsive element (IRE)-containing mRNA) is detected as an abundant 70 to 75 kD membrane protein. DMT1 is expressed in the cortex and not in the medulla, and is present at the brush border and apical pole of epithelial cells of proximal tubules. In contrast to the intestine, DMT1 protein expression in kidney is only slightly increased upon deprivation of dietary iron, suggesting different regulation at the two sites. In kidneys from mk/mk mice, the level of detectable DMT1(G185R) protein is drastically decreased compared to mk/+ controls.These results suggest that DMT1 may act as a re-uptake system for divalent cations at the brush border of kidney proximal tubules. A pathological mutation at DMT1 affects targeting/expression of the protein in the kidney.