New insights into NPP1 function: Lessons from clinical and animal studies

N C W Mackenzie, C Huesa, F Rutsch, V E Macrae

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The recent elucidation of rare human genetic disorders resulting from mutations in ectonucleotide pyrophosphotase/phosphodiesterase (ENPP1), also known as plasma cell membrane glycoprotein 1 (PC-1), has highlighted the vital importance of this molecule in human health and disease. Generalised arterial calcification in infants (GACI), a frequently lethal disease, has been reported in recessive inactivating mutations in ENPP1. Recent findings have also linked hypophosphataemia to a lack of NPP1 function. A number of human genetic studies have indicated that NPP1 is a vital regulator that influences a wide range of tissues through various signalling pathways and when disrupted can lead to significant pathology. The function of Enpp1 has been widely studied in rodent models, where both the mutant tiptoe walking (ttw/ttw) mouse and genetically engineered Enpp1(-/-) mice show significant alterations in skeletal and soft tissue mineralisation, calcium/phosphate balance and glucose homeostasis. These models therefore provide important tools with which to study the potential mechanisms underpinning the human diseases associated with altered NPP1. This review will focus on the recent advances in our current knowledge of the actions of NPP1 in relation to bone disease, cardiovascular pathologies and diabetes. A fuller understanding of the mechanisms through which NPP1 exerts its pathological effects may stimulate the development of novel therapeutic strategies for patients at risk from the devastating clinical outcomes associated with disrupted NPP1 function.
Original languageEnglish
Pages (from-to)961-968
Issue number5
Early online date31 Jul 2012
Publication statusPublished - 2012

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Bone Diseases/genetics
  • Bone Diseases/metabolism
  • Cardiovascular Diseases/genetics
  • Cardiovascular Diseases/metabolism
  • Humans
  • Phosphoric Diester Hydrolases/genetics
  • Phosphoric Diester Hydrolases/metabolism
  • Pyrophosphatases/genetics
  • Pyrophosphatases/metabolism


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