It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants—i.e.

[10] Michael S. Brown and Joseph L. Goldstein were awarded the 1985 Nobel Prize in Physiology or Medicine for their identification of LDL-R[11] and its relation to cholesterol metabolism and familial hypercholesterolemia.

[14] The N-terminal domain of the LDL receptor, which is responsible for ligand binding, is composed of seven sequence repeats (~50% identical).

Additionally, each repeat has highly conserved acidic residues which it uses to coordinate a single calcium ion in an octahedral lattice.

Both the disulfide bonds and calcium coordination are necessary for the structural integrity of the domain during the receptor's repeated trips to the highly acidic interior of the endosome.

The cytosolic C-terminal domain contains ~50 amino acids, including a signal sequence important for localizing the receptors to clathrin-coated pits and for triggering receptor-mediated endocytosis after binding.

[28] LDL receptors are translated by ribosomes on the endoplasmic reticulum and are modified by the Golgi apparatus before travelling in vesicles to the cell surface.

In humans, LDL is directly involved in the development of atherosclerosis, which is the process responsible for the majority of cardiovascular diseases, due to accumulation of LDL-cholesterol in the blood [citation needed].

A vast number of studies have described the relevance of LDL receptors in the pathophysiology of atherosclerosis, metabolic syndrome, and steatohepatitis.

[31] Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III.

[32][33] Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.