SLC25A51 is a mitochondrial membrane carrier protein that mediates the selective import of oxidized NAD+ into the mitochondrial matrix 1. This transport function is essential for maintaining mitochondrial NAD+ pools required for glycolysis and mitochondrial respiration 12. Loss of SLC25A51 decreases mitochondrial NAD+ content, impairs mitochondrial respiration, and blocks NAD+ uptake into isolated mitochondria, while overexpression increases mitochondrial NAD+ levels 1. SLC25A51 is the primary mammalian mitochondrial NAD+ transporter, with greater essentiality than its paralog SLC25A52 1. Clinically, SLC25A51 upregulation promotes cancer cell proliferation by sustaining mitochondrial acetylation homeostasis and proline biogenesis 3. In acute myeloid leukemia, elevated SLC25A51 expression correlates with poorer outcomes; its depletion increases apoptosis and prolongs survival in xenograft models 4. Additionally, SLC25A51 heterozygous loss impairs liver regeneration in mice, while hepatocyte-specific overexpression enhances regeneration comparably to NAD+ precursor supplements 5. Notably, SLC25A51 absence redirects NAD+ to cytoplasmic and nuclear compartments, enhancing PARP1-dependent DNA repair and reducing PARP inhibitor sensitivity 6. These findings identify SLC25A51 as both an attractive therapeutic target and potential vulnerability in cancer and regenerative medicine contexts.