To address the translational implication of this observation in PH and other cardiovascular diseases in vivo, the authors created an Ace2 S680D KI mouse line using CRISPR/Cas9 genomic editing to replace serine (S) with aspartic acid (D), resulting in a gain-of function mutation due to reduced ubiquitin-mediated degradation of Ace2 S680D mutant product20. This evidence concerns the gene ACE2 and cardiovascular disorder.