Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy is the most common hereditary CSVD, which is caused by a mutation of cysteine-altering in the NOTCH3 gene on chromosome 19, mainly due to mutations in the NOTCH3 extracellular domain (NOTCH3 ECD). Here, NOTCH3 is linked to Leukoencephalopathy.