The discovery of the role of MTP in mediating lipid transfer to apoB has greatly expanded our knowledge of the molecular mechanisms involved in apoB-containing lipoprotein assembly. In this review, advances referring to the structure, regulation and function of MTP are summarized and discussed. In addition to the well-known lipid transfer activity function, MTP has been shown to physically interact with apoB and this association appeared to be critically important in the regulation of lipoprotein production. Recent studies have provided insight into the paradoxical relationship between MTP polymorphism variants and metabolic disease. Genetic variants of MTP and their possible impact in the development of cardiovascular disease are discussed.