Extracellular nucleotide pyrophosphatase phosphodiesterase 1 (Enpp1) hydrolyzes extracellular ATP into AMP and PPi and may be an important source of extracellular PPi in the body [27, 28]. Enpp1 is the founding member of the ENPP or NPP family of enzymes . It has phosphodiesterase activity  and is a type II extracellular membrane bound glycoprotein located on the mineral-depositing matrix vesicles of osteoblasts and chondrocytes  and the vascular surface of cerebral capillaries . Enpp1 is also expressed in the kidney collecting duct and possibly other segments . The second source of PPi generation in the kidney is the mevalonate pathway inside mitochondria . Intracellular PPi is released into the interstitium and the urine by the transporter progressive ankylosis gene product (Ank) . Ank is located at the apical membrane of collecting ducts suggesting that it may function to inhibit mineralization within the tubule lumen. Additionally, ecto-5-prime nucleotidase (Nt5E/CD73), which inhibits Tnsalp by further hydrolyzing AMP to adenosine, and adenosine triphosphate-binding cassette , and subfamily C, member 6 (Abcc 6), recently shown to secrete ATP from hepatocytes , may both be involved in PPi generation.