NPP-type ectophosphodiesterases: unity in diversity

Trends Biochem Sci. 2005 Oct;30(10):542-50. doi: 10.1016/j.tibs.2005.08.005.


Nucleotide pyrophosphatase/phosphodiesterase (NPP)-type ectophosphodiesterases are found at the cell surface as type-I or type-II transmembrane proteins, but are also found extracellularly as secreted or shedded enzymes. They hydrolyze pyrophosphate or phosphodiester bonds in a variety of extracellular compounds including nucleotides, (lyso)phospholipids and choline phosphate esters. Despite their structurally related catalytic domain, each enzyme has well-defined substrate specificity. Catalysis by NPPs affects processes as diverse as cell proliferation and motility, angiogenesis, bone mineralization and digestion. In addition, there is emerging evidence for non-catalytic functions of NPPs in cell signaling. NPP-type ectophosphodiesterases are also implicated in the pathophysiology of cancer, insulin resistance and calcification diseases, and they hold great promise as easily accessible therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Neovascularization, Physiologic
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrophosphatases / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship
  • Substrate Specificity


  • Phosphoric Diester Hydrolases
  • Pyrophosphatases
  • nucleotide pyrophosphatase - phosphodiesterase I