ACE2 (angiotensin-converting enzyme 2) is a multifunctional membrane protein with critical roles in both systemic physiology and viral pathogenesis. Physiologically, ACE2 functions as a key counter-regulator of the renin-angiotensin-aldosterone system (RAAS), providing cardioprotective and pulmonary regulatory functions 1. The protein is highly expressed in heart, kidney, and lung tissues, where it regulates vascular function and inflammatory responses 1. ACE2's most clinically significant role is as the primary cell-surface receptor for SARS-CoV-2 viral entry 2. The spike protein of SARS-CoV-2 binds ACE2 through a well-characterized molecular interface that has shaped viral evolution 2. ACE2 expression is found in diverse tissues including salivary glands 3, oocytes 4, and spermatozoa 5, suggesting multi-route viral transmission potential. Notably, bat-infecting merbecovirus HKU5-CoV lineage 2 efficiently utilizes human ACE2 as a functional receptor, indicating zoonotic spillover risk 6. ACE2 expression is regulated by multiple mechanisms: transcriptional factors (STAT3, HNFs, GATA6), histone modifications, post-translational modifications including phosphorylation and SUMOylation, and ubiquitin-mediated degradation 7. In COVID-19, SARS-CoV-2 paradoxically upregulates ACE2 levels, enhancing host cell susceptibility 7. ACE2 dysregulation is associated with chrX diseases including hypertension, diabetes, and lung injury 7.