Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is a key part of the renin-angiotensin system (RAS) [1,2,5,6,9]. It maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury [1]. ACE2 also helps transport amino acids across the membrane [1]. Additionally, it is involved in regulating glycolipid metabolism in multiple tissues, such as the lungs, cardiovascular system, gastrointestinal tract, kidney, pancreas and adipose tissue [5].

In the context of COVID-19, ACE2 is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) [1,2,3,4,6,7,8,10]. SARS-COV-2 binding to ACE2 may lead to down-regulation of the membrane-bound enzyme, causing functional ACE2 deficiency, angiotensin imbalance, immune dysregulation and endothelial cell dysfunction [6]. Also, ACE2 levels are regulated by transcriptional, post-transcriptional, and post-translational regulation or modification [2]. Polymorphisms of ACE2 are associated with various diseases, including the severity of SARS-COV-2 infection [10].

In conclusion, ACE2 is essential for maintaining homeostasis, regulating metabolism and is a crucial factor in the pathophysiology of COVID-19. Understanding its functions and regulations through genetic models can provide insights into developing strategies for treating related diseases.