Electroneutral transporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis or immunity (PubMed:16638970, PubMed:18037372, PubMed:22563477, PubMed:24529376, PubMed:29337306). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation, a bicarbonate and a selenite anion or yet a metal cation and two bicarbonate anions (PubMed:16638970, PubMed:18037372, PubMed:22563477, PubMed:27166256). May also transport iron, mercury and cobalt through membranes (PubMed:16638970, PubMed:22898811, PubMed:24529376). Beside these endogenous cellular substrates, also imports cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:15722412, PubMed:16638970, PubMed:17108009, PubMed:18037372, PubMed:24529376). Through zinc import, indirectly regulates the metal-dependent transcription factor MTF1 and the expression of some metalloproteases involved in cartilage catabolism and also probably heart development (PubMed:24529376, PubMed:29337306). Also indirectly regulates the expression of proteins involved in cell morphology and cytoskeleton organization (PubMed:29927450). Indirectly controls innate immune function and inflammatory response by regulating zinc cellular uptake which in turn modulates the expression of genes specific of these processes (PubMed:23403290). Protects, for instance, cells from injury and death at the onset of inflammation (By similarity). By regulating zinc influx into monocytes also directly modulates their adhesion to endothelial cells and arteries (PubMed:30015240). At the apical membrane of hepatocytes, reclaims manganese from the bile and regulates, through the systemic levels of the nutrient, the activity of manganese-dependent enzymes (PubMed:28481222). Also participates in manganese reabsorption in the proximal tubule of the kidney (By similarity). By mediating the extracellular uptake of manganese by cells of the blood-brain barrier, may also play a role in the transport of the micronutrient to the brain. Through manganese cellular uptake also participates in mitochondrial proper function (By similarity). Finally, also probably functions intracellularly, translocating zinc from lysosome to cytosol to indirectly enhance the expression of specific genes during TCR-mediated T cell activation (By similarity). hydrogencarbonate(out) + selenite(out) + Zn(2+)(out) = hydrogencarbonate(in) + selenite(in) + Zn(2+)(in) 2 hydrogencarbonate(out) + Zn(2+)(out) = 2 hydrogencarbonate(in) + Zn(2+)(in) 2 hydrogencarbonate(out) + Mn(2+)(out) = 2 hydrogencarbonate(in) + Mn(2+)(in) Cd(2+)(out) + 2 hydrogencarbonate(out) = Cd(2+)(in) + 2 hydrogencarbonate(in) Fe(2+)(in) = Fe(2+)(out) Hg(2+)(in) = Hg(2+)(out) Co(2+)(in) = Co(2+)(out) Optimum pH is 7.5. Homodimer. Localizes to the lysosome of activated T-cells. A large fraction of the protein is found intracellularly in microvascular capillary endothelial cells that constitute the blood-brain barrier. Localized and functional at both apical and basolateral membranes of microvascular capillary endothelial cells that constitute the blood-brain barrier. Ubiquitously expressed. Expressed in the developing heart by cardiac endothelial cells with a peak of expression at 12.5 dpc and a decline to low levels in adult heart. Up-regulated in monocytes upon adhesion and recruitment to arteries (PubMed:30015240). Up-regulated by the pro-inflammatory cytokine interleukin-1 beta/IL1B (PubMed:24529376). N-glycosylated (PubMed:16638970). N-glycosylation is not required for proper iron and zinc transport (By similarity). The homozygous knockout of Slc39a8 is embryonic lethal by 16.5 dpc. Hearts exhibit hypertrabeculation and non-compaction phenotypes including excessive trabeculae and thin compact myocardium. These phenotypes are evident at 12.5 dpc and prominent at 14.5 dpc, and embryos that survive until 16.5 dpc display an even stronger phenotype. Ventricular septal defects are also observed. Some 14.5 dpc embryos exhibit body edema, suggesting that cardiac muscle function is compromised. Hearts display increased cardiomyocyte proliferation (PubMed:29337306). This is associated with decreased expression of metalloproteases and impaired degradation of the extracellular matrix leading to its aberrant accumulation in heart (PubMed:29337306). In mice homozygous for an hypomorphic allele of the gene, resulting in significant decreased expression of the protein, hematopoiesis and the development of multiple organs are affected from very early embryogenesis (PubMed:22563477). Conditional knockout of the gene at the level of the whole organism decreases manganese levels in tissues but has no effect on zinc and iron (PubMed:28481222). Conditional liver-specific knockout of the gene results in decreased systemic tissue manganese levels coupled to increased manganese in bile but has no effect on zinc or iron levels (PubMed:28481222). The decreased expression of the channel in testis vascular endothelial cells confers the resistance to cadmium-induced testicular damage trait to some mice strains. Belongs to the ZIP transporter (TC 2.A.5) family.