Whereas PCSK9 loss-of-function mutations carriers with lifelong reductions in LDL-C and coronary heart disease incidence, were not initially found at significantly reduced risk of stroke (3, 72), a much larger study of the UK Biobank database described the first genetic evidence of a protective effect of the R46L loss-of-function mutation on PCSK9 on ischemic stroke (73). Here, PCSK9 is linked to ischemic stroke.