If intracellular cholesterol uptake via the LDL receptor is involved in the pathogenesis of T2DM, then it would explain the hypothetical protection from diabetes in HeFH patients, but only in those with genetic defects affecting LDL receptor uptake, in contrast to the hypothesis that the protection would be dependent on the high plasma LDL-cholesterol concentrations observed in HeFH. The gene discussed is LDLR; the disease is type 2 diabetes mellitus.