Angiotensin-converting enzyme 2 (ACE2) is a receptor present in the human cardiovascular system as well as in the gut, kidneys, central nervous system, and adipose tissue. ACE2 is a negative regulator of the renin angiotensin system (RAS) mainly by converting Ang (angiotensin) I and Ang II into Ang 1–9 and Ang 1–7, respectively.

ACE2 has been shown to be involved in heart failure (HF), systemic and pulmonary hypertension (PH), myocardial infarction (MI), and diabetic cardiovascular complications where it may play a protective role. More recently it has been shown to be the receptor for SARS-CoV- and SARS-CoV-2 spike (S) proteins. Binding of S proteins to ACE2 initiates cellular entry via receptor-mediated internalization. SARS-CoV-2 spike (S) protein appears to bind ACE2 on host cells with significantly higher affinity than SARS-CoV-S. Following binding and internalisation ACE2 is degraded by proteolytic cleavage leading to loss of ACE2 function. This can further complicate the disease since although ACE2 facilitates viral entry to cells it also offers protection in acute lung injury. ACE2 is therefore a key target of interest in the fight against COVID-19.