ABCA1 and Tangier disease: Considering the recessive nature of Tangier disease, which necessitates loss-of-function variants in both ABCA1 alleles for clinical manifestation, and the fact that heterozygous carriers of loss-of-function variants generally exhibit only a 40%–50% reduction in HDL levels (8), the severe reduction in HDL-C levels observed in the p.R1901S patient would likely require functionally abnormal ABCA1 variants in both alleles, or other genetic factors to explain the phenotype.