SLC11A2 (DMT1) functions as a proton-coupled metal ion symporter that transports various divalent metal cations across cellular membranes with a 1:1 stoichiometry, showing selectivity for Cd(2+) > Fe(2+) > Co(2+), Mn(2+) >> Zn(2+), Ni(2+) 1. The transporter is essential for iron homeostasis by mediating intestinal iron absorption and transferrin-associated endosomal iron transport in erythroid precursors 2. SLC11A2 enables Fe(2+) and Mn(2+) entry into mitochondria, supporting heme synthesis and iron-sulfur cluster biogenesis 1. The protein localizes to late endosomes and lysosomes where it facilitates iron release from these compartments, representing a DMT1-independent pathway for cellular iron acquisition 2. Disease relevance includes associations with hypochromic microcytic anemia with iron overload, and disrupted SLC11A2 function contributes to iron accumulation in adipocytes during inflammation 3. In cancer contexts, SLC11A2 expression correlates with poor prognosis in ovarian cancer and promotes muscle wasting in pancreatic cancer cachexia through ferroptosis induction 45. The transporter is regulated by multiple microRNAs including miR-149-5p, miR-362-5p, and miR-539-5p, which modulate both gene expression and iron transport activity 6. Therapeutic targeting of SLC11A2 represents a promising approach for treating iron-related disorders and certain cancers.