Cell type- and tissue-specific functions of ecto-5'-nucleotidase (CD73)

Am J Physiol Cell Physiol. 2019 Dec 1;317(6):C1079-C1092. doi: 10.1152/ajpcell.00285.2019. Epub 2019 Aug 28.


Ecto-5'-nucleotidase [cluster of differentiation 73 (CD73)] is a ubiquitously expressed glycosylphosphatidylinositol-anchored glycoprotein that converts extracellular adenosine 5'-monophosphate to adenosine. Anti-CD73 inhibitory antibodies are currently undergoing clinical testing for cancer immunotherapy. However, many protective physiological functions of CD73 need to be taken into account for new targeted therapies. This review examines CD73 functions in multiple organ systems and cell types, with a particular focus on novel findings from the last 5 years. Missense loss-of-function mutations in the CD73-encoding gene NT5E cause the rare disease "arterial calcifications due to deficiency of CD73." Aside from direct human disease involvement, cellular and animal model studies have revealed key functions of CD73 in tissue homeostasis and pathology across multiple organ systems. In the context of the central nervous system, CD73 is antinociceptive and protects against inflammatory damage, while also contributing to age-dependent decline in cortical plasticity. CD73 preserves barrier function in multiple tissues, a role that is most evident in the respiratory system, where it inhibits endothelial permeability in an adenosine-dependent manner. CD73 has important cardioprotective functions during myocardial infarction and heart failure. Under ischemia-reperfusion injury conditions, rapid and sustained induction of CD73 confers protection in the liver and kidney. In some cases, the mechanism by which CD73 mediates tissue injury is less clear. For example, CD73 has a promoting role in liver fibrosis but is protective in lung fibrosis. Future studies that integrate CD73 regulation and function at the cellular level with physiological responses will improve its utility as a disease target.

Keywords: extracellular adenosine; fibrosis; hypoxia; inflammation; ischemia-reperfusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • 5'-Nucleotidase / deficiency
  • 5'-Nucleotidase / genetics*
  • Adenosine / metabolism
  • Adenosine Monophosphate / metabolism
  • Animals
  • Arteries / metabolism
  • Arteries / pathology
  • Calcinosis / genetics*
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • GPI-Linked Proteins / deficiency
  • GPI-Linked Proteins / genetics
  • Gene Expression Regulation
  • Heart Failure / genetics*
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Homeostasis
  • Humans
  • Mutation, Missense
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Organ Specificity
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Respiratory System / metabolism
  • Respiratory System / pathology


  • GPI-Linked Proteins
  • Adenosine Monophosphate
  • 5'-Nucleotidase
  • NT5E protein, human
  • Adenosine