Abstract-The production of apolipoprotein B (apoB)-containing lipoproteins by the liver is regulated by a complex series of processes involving apoB being cotranslationally translocated across the endoplasmic reticulum and assembled into a lipoprotein particle. The translocation of apoB across the endoplasmic reticulum is facilitated by the intraluminal chaperone, microsomal triglyceride transfer protein (MTP). MTP facilitates the translocation and folding of apoB, as well as the addition of lipid to lipid-binding domains (which consist of amphipathic  sheets and ␣ helices). In the absence of MTP or sufficient lipid, apoB exhibits translocation arrest. Thus, apoB translation, translocation, and assembly with lipids to form a core-containing lipoprotein particle occur as concerted processes. Abrogation of Ն1 of these processes diverts apoB into a degradation pathway that is dependent on conjugation with ubiquitin and proteolysis by the proteasome. The nascent core-containing lipoprotein particle that forms within the lumen of the endoplasmic reticulum can be "enlarged" to form a mature very low density lipoprotein particle. Additional studies show that the assembly and secretion of apoB