LDLRAP1 contains a phosphotyrosine binding (PTB) domain that interacts with the cytoplasmic tail of the LDL receptor . This interaction is essential for the efficient internalization of LDLR-LDL complexes from coated pits, which are specialized regions of the plasma membrane involved in receptor-mediated endocytosis . The protein binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface, thereby stabilizing the interaction between the receptor and the structural components of the pits .
Mutations in the LDLRAP1 gene can lead to autosomal recessive hypercholesterolemia (ARH), a disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) in the blood . This condition increases the risk of cardiovascular diseases, such as atherosclerosis and coronary artery disease . The malfunction of LDLR due to these mutations impairs the body’s ability to remove LDL-C from the bloodstream, leading to its accumulation .
The study of LDLRAP1 is significant for understanding and potentially treating hypercholesterolemia and related cardiovascular diseases . By exploring the mechanisms of LDLRAP1 and its interactions with LDLR, researchers aim to develop targeted therapies that can enhance the clearance of LDL-C from the bloodstream .
Human recombinant LDLRAP1 is used in research to study its role in cholesterol metabolism and its potential therapeutic applications . Recombinant proteins are produced through genetic engineering techniques, allowing scientists to investigate the protein’s structure, function, and interactions in a controlled environment .