PCSK9 and homozygous familial hypercholesterolemia: This effect may be due to intracellular cholesterol depletion caused by statin‐induced activation of SREBP‐2, which, in turn, upregulates expression of both the LDL receptor and PCSK9 genes, leading to elevated circulating levels of PCSK9.25 Interestingly, PCSK9 levels increased variably in response to statin therapy in only 50% of HoFH patients, whereas levels rose steadily in the majority of HeFH patients.