ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:31341297). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31489369, PubMed:31341297). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (PubMed:31341297). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A5/ANT2 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (PubMed:31341297). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (PubMed:31341297). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (PubMed:31341297). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31489369). It is however unclear if SLC25A5/ANT2 constitutes a pore-forming component of mPTP or regulates it (PubMed:31489369). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756). As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (By similarity). ADP(in) + ATP(out) = ADP(out) + ATP(in) H(+)(in) = H(+)(out) The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297). Monomer (By similarity). Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5/ANT2. Interacts with AK4 (By similarity). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756). May localize to non-mitochondrial membranes. Widely expressed. The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue. Trimethylated by ANTKMT at Lys-52. Mice show an apparently normal embryonic development except pale phenotype, but show a reduced birth rate (PubMed:25613378). Postnatal growth is severely retarded with macrocytic anemia, B lymphocytopenia, lactic acidosis and bloated stomach, causing lethality within 4 weeks (PubMed:25613378). Mice develop anemia in a cell-autonomous manner by maturation arrest of erythroid precursors with increased reactive oxygen species and premature deaths (PubMed:25613378). B-lymphocyte development is also affected: splenocytes show a reduction in maximal respiration capacity and cellular ATP levels as well as an increase in cell death accompanying mitochondrial permeability transition pore opening (PubMed:25613378). Cells display impaired mitochondrial uncoupling (PubMed:31341297). Cells show impaired autophagy, leading to accumulation of aberrant mitochondria (PubMed:31618756). Mice lacking Slc25a4/Ant1 and Slc25a5/Ant2 in liver still have mitochondrial permeability transition pore (mPTP) activity, although more Ca(2+) is required to activate the mPTP (PubMed:14749836). Deletion of Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4 in liver completely inhibits mPTP (PubMed:31489369). Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca(2+)-induced mPTP formation (PubMed:31489369). Belongs to the mitochondrial carrier (TC 2.A.29) family. It is unclear if SLC25A4/ANT1 constitutes a pore-forming component of mitochondrial permeability transition pore (mPTP) (PubMed:14749836, PubMed:31489369). Initial reports, based on deletion of Slc25a4/Ant1 and Slc25a5/Ant2, suggested that ADP/ATP translocase rather acts as a regulator of mPTP (PubMed:14749836). However, deletion of all ADP/ATP translocase components (Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4) completely inhibits mPTP, suggesting that ADP/ATP translocase constitutes a pore-forming component of mPTP (PubMed:31489369). Discrepancy between reports may be caused by overexpression of Slc25a31/Ant4 in mice lacking Slc25a4/Ant1 and Slc25a5/Ant2, which compensates for the loss of Slc25a4/Ant1 and Slc25a5/Ant2 (PubMed:31489369).