HTRA1 and cerebral small vessel disease: Human genetics studies identified the loss of HTRA1 proteolytic function as causative of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (OMIM #600142), and autosomal dominant mutations in the protease domain of HTRA1 were also linked to late-onset cerebral small vessel disease (Fukutake, 2011; Uemura et al., 2020; Verdura et al., 2015).