ANKH is a transmembrane transporter protein that exports ATP and other nucleoside triphosphates from the cytosol to the extracellular space, playing a central role in regulating local inorganic pyrophosphate (PPi) levels in peripheral tissues 1. The protein prevents pathologic joint mineralization by maintaining adequate extracellular PPi concentrations, which inhibit calcium pyrophosphate crystal formation 2. ANKH expression is regulated by intracellular oxygen, phosphate, calcium levels, and TGF-β signaling, and the protein interacts with multiple cellular components including phosphate transporters and NF-κB signaling proteins 3. Additionally, ANKH regulates extracellular levels of citrate and other TCA cycle intermediates essential for bone osteogenic differentiation and strength. Mutations in ANKH cause familial calcium pyrophosphate deposition disease (CPPD) by enhancing protein activity and elevating extracellular PPi, promoting pathologic crystal deposition and inflammatory arthritis 1. ANKH variants are also associated with craniometaphyseal dysplasia and represent genetic risk factors for sporadic CPPD 4. Notably, protective ANKH alleles are enriched in cognitively healthy centenarians, suggesting a role in neuroprotection against Alzheimer's disease through immune and endolysosomal pathways 5. Beyond mineralization disorders, ANKH influences chondrogenesis, osteoblastogenesis, and osteoclastogenesis, indicating broader significance in skeletal biology.