but not LDL. This inability to bind LDL is due to VLDLR's incapability to bind apolipoprotein B (apoB), which is present in LDL. Inhibitors Receptor-associated protein (RAP) and thrombospondin-1 (THBS1) have been identified as compounds that bind VLDLR. In many cases, these compounds exhibit inhibitory effects. THBS1 binds VLDLR and blocks ligand binding. This plays an important role in the reelin pathway, as THBS1 can block the attachment of reelin, while simultaneously stimulating the transcription factors normally activated by reelin. This binding of THBS1, however, does not induce the subsequent degradation of these transcription factors, as reelin does, and can thus lead to greatly amplified effects. The RAP protein acts similarly by blocking reelin from binding VLDLR. However, in this case phosphorylation of transcription factors, usually performed by reelin, is also blocked. Tissue distribution and expression VLDLR is found throughout the body, with particularly high expression in fatty acid tissues due to their high level of triglycerides, VLDLR’s primary ligand. These tissues include those of the heart, skeletal muscle, and adipose layer. In addition, the receptor is found in macrophages, endothelial cells of capillaries, and in the brain, where it has a very different function from that found in the rest of the body. There is a preferred expression for VLDLR type I in the heart, skeletal muscle and brain, as opposed to type II, which is mainly expressed in non-muscular tissues including the cerebrum, cerebellum, kidney, spleen, and aortic endothelial cells. The highest expression of VLDLR is found in the brain. Although VLDLR is found in almost all regions of the brain, its highest expression is restricted to the cortex and cerebellum. Here, the receptor can be found on resting or activated microglia that are associated with senile plaques and cortical neurons, neuroblasts, matrix cells, Cajal-Retzius cells, glioblasts, astrocytes, oligodendrocytes, and region-specific pyramidal neurons. Despite its major role in cholesterol and fatty acid metabolism, VLDLR is not found in the liver. This phenomenon is mainly attributed to the very high levels of LDLR in these areas. In addition, it has been uncovered that this receptor is found, sub-cellularly, in the non-lipid raft sections of cell membranes. Regulation Unlike LDLR, VLDLR does not exhibit any feedback mechanism, and hence intracellular lipoproteins are incapable of regulating it. This phenomenon is due to a difference in the sterol regulatory element-1 (SRE-1) of VLDLR. Normal SRE-1 sequences, like those found in LDLR, are