Despite this knowledge on its role in lipoprotein uptake, the complete mechanism of lipid metabolism performed by VLDLR is not fully understood. Endocytosis VLDLR is known to employ endocytosis, although the exact mechanism of this process is unknown for this protein. Endocytosis is mediated through NPxY sequences known to signal for receptor internalization through clathrin-coated pits. The presence of this sequence in the cytoplasmic tail of VLDLR makes endocytosis possible. In general, lipoprotein receptors undergo a process by which they are endocytosed with their ligand into clathrin-coated pits. From here, they are together transported to early and late endosomes until reaching the lysosome. At this point, hydrolysis occurs and lipoprotein is released into the cytoplasm while the receptors are recycled back to the cell surface. It is not yet confirmed if VLDLR follows this exact mechanism, but one closely related to it is likely. In the nervous system In addition to its role throughout the body, VLDLR has a unique role in the brain. It is a key component of the reelin pathway, which functions on one hand side in neuronal migration during the development of the brain, on the other hand in the retention of new memory traces in the hippocampal formation. VLDLR links the reelin protein to an intracellular signaling protein, Dab1, that tells the individual neurons where to go within the anatomy of the brain. Mutations in VLDLR often do not lead to major disorganization as seen in reelin mutations. However, a VLDLR mutation does lead to some disorganization primarily located in the cerebellum, where VLDLR is believed to be most prominent. Neuronal migration VLDLR is expressed on migrating neurons to help guide them to their proper location in the brain. This process is part of the reelin pathway, which is responsible for the inside-out formation of the six-layered neocortex. Despite the discovery of this pathway, many of the specifics and molecular mechanisms of this process are still being debated. The presence of two reelin receptors, VLDLR and ApoER2, has made it difficult to distinguish each protein’s specific function. VLDLR is primarily responsible for the correct layering of pyramidal cells into layer 1 of the cerebral cortex. In particular, the absence of VLDLR may lead to ectopic accumulation of pyramidal cells in this region. VLDLR does not affect the migration of early born cells into an organized layer, but since its absence results in the invasion of