HTRA1 is a homotrimeric serine protease that is expressed in endothelial and smooth muscle cells of the vasculature.26–28 Biallelic loss-of-function variants cause arteriopathy in the cerebral circulation, which presents clinically with premature stroke and early-onset vascular dementia.28 Rare, predicted damaging missense variants (Rare Exome Variant Ensemble Learner score >0.5) were associated with ≈50% increase in the odds of ASCVD (OR, 1.54 [95% CI, 1.32–1.80]; P=4.9×10−8). The gene discussed is HTRA1; the disease is arterial disorder.