Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels. PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals. Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (By similarity). Appears to modulate insulin sensitivity. Also involved in melanogenesis (By similarity). Also able to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (By similarity). 2',3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2',3'-cGAMP hydrolysis is therefore unclear. Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3'-3'-cGAMP (By similarity). Hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides. a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-phosphate + diphosphate + H(+) ATP + H2O = AMP + diphosphate + H(+) H2O + UTP = diphosphate + H(+) + UMP GTP + H2O = diphosphate + GMP + H(+) CTP + H2O = CMP + diphosphate + H(+) 2',3'-cGAMP + 2 H2O = AMP + GMP + 2 H(+) H2O + P(1),P(4)-bis(5'-adenosyl) tetraphosphate = AMP + ATP + 2 H(+) 3',5'-cyclic AMP + H2O = AMP + H(+) Binds 2 Zn(2+) ions per subunit. At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis. Ectonucleotide pyrophosphatase/phosphodiesterase family member 1: Homodimer (By similarity). Ectonucleotide pyrophosphatase/phosphodiesterase family member 1: Interacts with INSR; leading to inhibit INSR autophosphorylation and subsequent activation of INSR kinase activity (By similarity). Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form: Monomeric (By similarity). Targeted to the basolateral membrane in polarized epithelial cells and in hepatocytes, and to matrix vesicles in osteoblasts. Secreted following proteolytic cleavage. The di-leucine motif is required for basolateral targeting in polarized epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells. The secreted form is produced through cleavage at Lys-85 by intracellular processing. Belongs to the nucleotide pyrophosphatase/phosphodiesterase family. It is uncertain whether Met-1 or Met-35 is the initiator.