NOTCH3 mutations in CADASIL lead to (cerebro)vascular NOTCH3 protein aggregation and compromised cerebral blood flow, with more than 200 distinct NOTCH3 mutations identified in CADASIL [8,9]. The majority of individuals with a NOTCH3 variant will develop NOTCH3-associated SVD after the age of 65; therefore, NOTCH3 should be considered as a genetic risk factor in SVD risk stratification and prevention [9]. The gene discussed is NOTCH3; the disease is snowflake vitreoretinal degeneration.