A Test in Context: Neprilysin: Function, Inhibition, and Biomarker

Antoni Bayes-Genis, Jaume Barallat, A. Mark Richards

Research output: Contribution to journalReview articleResearchpeer-review

148 Citations (Scopus)


© 2016 American College of Cardiology Foundation Neprilysin is a zinc-dependent endopeptidase. It is ubiquitous in distribution and promiscuous in function, with >50 putative peptide substrates with varying levels of in vitro and/or in vivo evidence of functional relevance. In the first part of this review, we discuss the genetic, structural, substrate, and pathophysiological aspects of neprilysin. We incorporate information provided by genetically modified models, as well as pre-clinical and clinical data from investigations of synthetic neprilysin inhibitors. We next highlight the value of neprilysin as a biotarget and weigh the clinical benefits of synthetic neprilysin inhibitors, either alone or in combination with antagonists of the renin–angiotensin system. Finally, we provide evidence about soluble neprilysin as a biomarker surrogate in patients with heart failure and identify important gaps that require further research before soluble neprilysin is used clinically. In sum, neprilysin is a versatile, veteran player returning yet again to center stage after an eventful career spanning >40 years.
Original languageEnglish
Pages (from-to)639-653
JournalJournal of the American College of Cardiology
Issue number6
Publication statusPublished - 9 Aug 2016


  • amyloid-beta peptides
  • angiotensin receptor-neprilysin inhibitor
  • endopeptidases
  • heart failure
  • natriuretic peptides
  • renin–angiotensin system


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