ACE2 is an integral membrane metalloproteinase that regulates the renin-angiotensin system (Tikellis et al., 2011). Both SARS-CoV-1 and SARS-CoV-2 have co-opted ACE2 to function as the receptor by which these viruses attach and fuse with host cells (Hoffmann et al., 2020; Li et al., 2003). ACE2 is cleavable by ADAM proteases at the cell surface (Lambert et al., 2005), resulting in the shedding of a soluble ectodomain that can be detected in apical secretions of various epithelial layers (gastric, airway, etc.) and in serum (Epelman et al., 2009). The N-terminal extracellular domain of ACE2 contains six canonical sequons for N-linked glycosylation and several potential O-linked sites. Several nonsynonymous single-nucleotide polymorphisms (SNPs) in the ACE2 gene have been identified in the human population and could potentially alter ACE2 glycosylation and/or affinity of the receptor for the viral Spike protein (Li et al., 2005). Given that glycosylation can affect the half-life of circulating glycoproteins in addition to modulating the affinity of their interactions with receptors and immune/inflammatory signaling pathways (Marth and Grewal, 2008; Varki, 2017), understanding the impact of glycosylation of ACE2 with respect to its binding of SARS-CoV-2 Spike glycoprotein is of high importance. The proposed use of soluble extracellular domains of ACE2 as decoy, competitive inhibitors for SARS-CoV-2 infection emphasizes the critical need for understanding the glycosylation profile of ACE2 so that optimally active biologics can be produced (Lei et al., 2020; Monteil et al., 2020).