Ectonucleotide pyrophosphatase-phosphodiesterase 1 (ENPP1) is a single-pass, type II transmembrane protein primarily involved in ATP hydrolysis at the plasma membrane. Targeting of ENPP1 to the basolateral cell surface relies on the presence of a carboxy-terminal di leucine-based signal. ENPP1 plays important roles in bone mineralization and soft tissue calcification. Mutations in the corresponding ENPP1 gene cause generalized arterial calcification in infancy (GACI) and idiopathic infantile arterial calcification (IIAC). ENPP1 inhibits insulin receptor function and overexpression of this enzyme causes insulin resistance and glucose intolerance in mice. Genetic variants of ENPP1 have been associated with obesity and type 2 diabetes.
