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Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2)
  1. Owen Wiese1,
  2. Annalise E Zemlin1,
  3. Tahir S Pillay2,3
  1. 1 Division of Chemical Pathology, Faculty of Health Sciences, Stellenbosch University & National Health Laboratory Service (NHLS), Cape Town, South Africa
  2. 2 Department of Chemical Pathology, University of Pretoria & National Health Laboratory Service (NHLS), Pretoria, South Africa
  3. 3 Division of Chemical Pathology, University of Cape Town, Cape Town, South Africa
  1. Correspondence to Professor Tahir S Pillay, Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria 0007, South Africa; jclinpatheic{at}


The renin–angiotensin system is mainly associated with the regulation of blood pressure, but recently many other functions of this system have been described. ACE2, an 805-amino acid monocarboxypeptidase type I transmembrane glycoprotein, was discovered in 2000 and has sequence similarity to two other proteins, namely ACE and collectrin. The ACE2 gene is located on Xp22 and is highly polymorphic. ACE2 is expressed in numerous tissues especially the lung alveolar epithelial cells, heart, kidney and gastrointestinal tract. Animal studies have found that ACE2 is central in diseases affecting almost all organ systems, among other cardiac, respiratory, renal and endocrine functions. ACE2 was identified as the cellular contact point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the global pandemic (COVID-19), and is a potential drug target. SARS-CoV-2 infection has several effects on the renin–angiotensin system and conversely, regulation of this receptor may affect the progress of infection. We describe the genetics and functions of ACE2, explore its various physiological functions in the renin–angiotensin system and discuss its role in the pathophysiology of disease. ACE2 opposes the vasopressor ACE pathway of the renin–angiotensin system by converting angiotensin (Ang) I to Ang (1–9) and Ang II to Ang (1–7) which initiates the vasodilatory pathway. ACE2 may have a protective effect in the lung and kidney as knockout mice display susceptibility to acute respiratory distress and hypertensive nephropathy. Binding of SARS-CoV-2 and the subsequent fusion and downregulation of this pathway during SARS-CoV-2 infection may explain some of the unusual sequelae seen in COVID-19.

  • viruses
  • inflammation
  • kidney
  • lung
  • infections

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  • Handling editor Des Richardson.

  • Contributors OW wrote the first and subsequent drafts and prepared the figures. AEZ co-wrote and reviewed the first draft. TSP conceived the idea for the manuscript, reviewed and amended the revisions of the first draft and figures and prepared the final manuscript and references. Images created with

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.