PCSK9 and Hypercholesterolemia: For instance, the discovery of PCSK9 (proprotein convertase subtilisin/kexin type 9) loss-of-function mutations, which confer lifelong protection against atherosclerosis and coronary heart disease (CHD) without discernible deficits in homozygous carriers (Cohen et al., 2005), provided a compelling “failsafe rationale” for the development of antibodies and small interfering RNAs (siRNAs) against PCSK9, or even gene editing for the treatment of hypercholesterolemia and prevention of atherosclerosis (Nurnberg et al., 2016; Musunuru et al., 2018; King et al., 2019).