Microsomal triglyceride transfer protein (MTTP) (MTTP)

Microsomal triglyceride transfer protein (MTTP) is a critical chaperone protein located within the lumen of the endoplasmic reticulum in hepatocytes and enterocytes. Its primary biological function is to facilitate the transfer of lipids, including triglycerides and phospholipids, onto nascent apolipoprotein B (apoB) to form very-low-density lipoproteins (VLDL) in the liver and chylomicrons in the small intestine [UniProt: P55157, NCBI Gene: 4547]. Because MTTP is essential for the secretion of these atherogenic lipoproteins, it has become a significant therapeutic target for severe dyslipidemias such as homozygous familial hypercholesterolemia (HoFH). Targeting MTTP at the mRNA level using antisense oligonucleotides (e.g., ISIS 353512) or at the protein level using small molecules (e.g., Lomitapide) effectively lowers plasma LDL-cholesterol and apoB levels [PubMed: 17684133]. However, the inhibition of MTTP prevents the export of lipids from the liver, frequently leading to hepatic steatosis and elevated liver enzymes, which limits its clinical utility to high-risk patient populations. Furthermore, intestinal inhibition of MTTP often results in significant gastrointestinal side effects due to malabsorption of dietary fats [PubMed: 23434151].

Other names

MTPMicrosomal triglyceride transfer protein large subunitABLMTTP mRNAMicrosomal triglyceride transfer protein gene

Antisense oligonucleotide-mediated degradation of MTTP mRNA or small molecule inhibition of the MTTP protein, leading to reduced assembly and secretion of apolipoprotein B-containing lipoproteins (VLDL and chylomicrons) from the liver and intestines [PubMed: 17684133, PubMed: 23434151].