PCSK9 and Hypercholesterolemia: This important finding was later reaffirmed by Horton and colleagues and the recognition of statins’ capacity to intensify PCSK9 transcription.53,65 Interestingly, while the deficiency of cholesterol and the application of statin treatment positively regulated both PCSK9 and LDLR mRNA levels, PCSK9 itself could effectively degrade LDLR protein, which could explain the mechanism underlying certain reported human mutations leading to hypercholesterolemia.