Third, there are at least several genetic factors, such as rare variants of ATP binding cassette subfamily G member 5 (ABCG5), ATP binding cassette subfamily G member 8 (ABCG8), and apolipoprotein E (APOE), that are contributing to worsen their phenotypes of HeFH, making it difficult to differentiate them from patients with HoFH. Here, APOE is linked to homozygous familial hypercholesterolemia.