ANKH inorganic pyrophosphate transport regulator (ANKH)

The ANKH inorganic pyrophosphate transport regulator is a multipass transmembrane protein primarily responsible for exporting inorganic pyrophosphate (PPi) from the cytosol to the extracellular matrix. By regulating extracellular PPi levels, ANKH prevents hydroxyapatite and calcium phosphate crystal formation in soft tissues and joints, acting as a key gatekeeper against pathological calcification. The protein is essential for normal skeletal development and bone remodeling, influencing both osteoblast and osteoclast differentiation. Mutations in ANKH can lead to inherited diseases such as craniometaphyseal dysplasia (characterized by excessive bone growth) and familial forms of calcium pyrophosphate deposition disease (producing painful joint inflammation and cartilage degeneration). ANKH also exports ATP—which is converted to PPi by extracellular ecto-enzymes—and may transport additional metabolic intermediates like citrate, important for bone matrix integrity. Its expression and function are tightly regulated; disruption can result in a spectrum of mineralization disorders affecting joints, skeleton, and in some cases, vascular tissues. Its biological importance makes ANKH a potential, though currently experimental, therapeutic target in calcification disorders.

Other names

Progressive ankylosis protein homologProgressive ankylosis gene product (ANK in mouse, ANKH in human)ANK (commonly used, but should be distinguished from the human gene/protein ANKH)

Drugs (such as probenecid) inhibit the export of ATP and/or PPi from cells, thereby altering extracellular PPi concentrations and influencing tissue mineralization