Apolipoproteins are proteins that bind lipids to form lipoproteins, which carry fats and cholesterol in the bloodstream. Apolipoproteins provide structural support to these lipoproteins, may act as ligands for specific cell surface receptors or may modulate the activity of metabolic enzymes that act on lipoproteins. A major class of apolipoproteins is ApoB, which is found in two forms: ApoB-100 (550 kDa) and ApoB-48 (264 kDa). ApoB-48 is made from the N-terminal 48% of the Apolipoprotein B-100 protein due to a post-transcriptional mRNA editing by the ApoB mRNA editing enzyme ApoBec1. ApoBec1 causes a C to U transition, replacing a CAA glutamine encoding codon for a UAA stop codon and generating ApoB-48. ApoBec1 is expressed in the intestine but not the liver, thus ApoB-48 is secreted by the intestine to become the building block of chylomicrons, while ApoB-100 is secreted by the liver to become a component of very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). Importantly, ApoB is also post-translationally palmitoylated; palmitoylation is necessary for proper assembly of lipoproteins (including proper assembly of the hydrophobic core). Furthermore, ApoB-100 operates on the surface of LDLs to allow binding to the LDL receptor and transport for breakdown of LDLs.

Mutations in the Apolipoprotein B gene can cause several diseases. First, in familial hypobetalipoproteinemia (FHBL), mutations in the Apolipoprotein B gene cause production of abnormally short lengths of ApoB protein, lowering the amount of lipoproteins and hence decreasing the body’s capacity to transport and absorb fat and fat-soluble vitamins. Second, in a form of inherited hypercholesterolemia called familial defective ApoB-100 (FDB), mutations in the Apolipoprotein B gene prevent LDLs from effectively binding to their receptors. As a result, fewer LDLs are removed from the blood, leading to hypercholesterolemia, distribution and buildup of cholesterol into tissues such as the skin and arteries, and an increased risk of coronary artery disease (CAD).