According to the response-to- retention hypothesis of atherosclerosis proposed by Williams and Tabas, diffusion of circulating positively-charged apoB-containing lipoproteins into the intima, which is based on non LDL-receptor (LDLR)-dependent mechanisms (Jang et al., 2020), and occurs particularly in the presence of elevated circulating LDL cholesterol (LDL-C) such as in familial hypercholesterolemia, over a lifetime results in their infiltration into and retention in the subendothelial space (Williams and Tabas, 1995). Here, LDLR is linked to familial hypercholesterolemia.