Apolipoprotein B (ApoB) is a protein that in humans is encoded by the APOB gene. Its measurement is commonly used to detect the risk of atherosclerotic cardiovascular disease.

The protein occurs in the plasma in two main isoforms, ApoB48 and ApoB100. The first is synthesized exclusively by the small intestine, the second by the liver. ApoB-100 is the largest of the apoB group of proteins, consisting of 4563 amino acids, including a 27-amino acid signal peptide and a 4536-amino acid mature protein. Both isoforms are coded by APOB and by a single mRNA transcript larger than 16 kb. ApoB48 is generated when a stop codon (UAA) at residue 2153 is created by RNA editing. There appears to be a trans-acting tissue-specific splicing gene that determines which isoform is ultimately produced.^{[citation needed]} Alternatively, there is some evidence that a cis-acting element several thousand bp upstream determines which isoform is produced.^{[citation needed]}

As a result of the RNA editing, ApoB48 and ApoB100 share a common N-terminal sequence, but ApoB48 lacks ApoB100's C-terminal LDL receptor binding region. ApoB48 is named because it constitutes 48% of the sequence for ApoB100. ApoB48 is a unique protein in chylomicrons from the small intestine. After most of the lipids in the chylomicron have been absorbed, ApoB48 returns to the liver as part of the chylomicron remnant, where it is endocytosed and degraded.

Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, Lp(a), IDL, and LDL particles (LDL—commonly known as "bad cholesterol" when in reference to both heart disease and vascular disease in general), which is responsible for carrying fat molecules (lipids), including cholesterol, around the body to all cells within all tissues. While all the functional roles of ApoB within the LDL (and all larger) particles remain somewhat unclear, it is the primary organizing protein (of the entire complex shell enclosing/carrying fat molecules within) component of the particles and is absolutely required for the formation of these particles. What is also clear is that the ApoB on the LDL particle acts as a ligand for LDL receptors in various cells throughout the body (i.e., less formally, ApoB indicates fat-carrying particles are ready to enter any cells with ApoB receptors and deliver fats carried within into the cells).

Very low-density lipoproteins and low-density lipoproteins interfere with the quorum sensing system that upregulates genes required for invasive Staphylococcus aureus infection. The mechanism of antagonism entails binding ApoB to a S. aureus autoinducer pheromone, preventing signaling through its receptor. Mice deficient in ApoB are more susceptible to invasive bacterial infection.

There is considerable evidence that concentrations of ApoB and especially the NMR assay (specific for LDL-particle concentrations) are superior indicators of vascular/heart disease driving physiology than either total cholesterol or LDL-cholesterol (as long promoted by the NIH starting in the early 1970s). However, primarily for historic cost/complexity reasons, cholesterol, and estimated LDL-cholesterol by calculation, remains the most commonly promoted lipid test for the risk factor of atherosclerosis. ApoB is routinely measured using immunoassays such as ELISA or nephelometry. Refined and automated NMR methods allow measurement distinctions between the many different ApoB particles.

High levels of ApoB are related to heart disease. Hypobetalipoproteinemia is a genetic disorder that can be caused by a mutation in the ApoB gene, APOB. Abetalipoproteinaemia is caused by a mutation in the microsomal triglyceride transfer protein gene, MTTP.

Mutations in gene APOB100 can also cause familial hypercholesterolemia, a hereditary (autosomal dominant) form of metabolic disorder hypercholesterolemia.