PCSK9 and familial hypercholesterolemia: Although the prevalence of genetically defined hypercholesterolemia varies across studies (8), a substantial proportion of hypercholesterolemic subjects do not have mutations in LDLR, APOB, or PCSK9. A major reason for this finding could be the presence of disease-causing mutations in other genes involved in cholesterol homeostasis either affecting the LDLR pathway or other yet to be defined mechanisms.