Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:17962486). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:17962486). Functions at acidic pH via alternate outward- and inward-open conformation states (By similarity). Protonation of residues in the outward open state primes the protein for transport (By similarity). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (By similarity). Also able to transport antifolate drugs, such as methotrexate and pemetrexed (PubMed:17962486). Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes (By similarity). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (PubMed:16143108). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (PubMed:22058337). Hence, participates in the trafficking of heme and increases intracellular iron content (By similarity). folate(in) + H(+)(in) = folate(out) + H(+)(out) (6S)-5-methyl-5,6,7,8-tetrahydrofolate(in) + H(+)(in) = (6S)-5-methyl-5,6,7,8-tetrahydrofolate(out) + H(+)(out) H(+)(in) + methotrexate(in) = H(+)(out) + methotrexate(out) H(+)(in) + pemetrexed(in) = H(+)(out) + pemetrexed(out) Shifts from the apical membrane of intestinal cells iron-deficient cells to the cytoplasm in response to increased in iron stores (PubMed:16143108). Localizes to the basolateral membrane of choroid plexus (PubMed:19074442). Highly expressed in duodenum, especially in duodenal mucosa, the main site of intestinal heme absorption (PubMed:16143108). Expressed in the retina and retinal pigment epithelium (PubMed:17962486, PubMed:22058337). Weakly expressed in the kidney (PubMed:16143108). Not expressed in duodenum before weaning or in placenta (PubMed:16143108). Weakly or not expressed in brain, heart, lung, skeletal muscle, testis and neonatal liver (PubMed:16143108). Up-regulated in response to hypoxia, it is however unclear whether such up-regulation is direct or not (PubMed:16143108). Not induced in the duodenum of iron-deficient mice (PubMed:16143108). Deletion mutant mice develop severe macrocytic normochromic anemia and ineffective erythropoiesis (PubMed:21346251). More than 90% of mice die by 10 to 12 weeks of age (PubMed:21346251). Belongs to the major facilitator superfamily. SLC46A family.