exon than encoded by LDLR. This extra exon in the VLDLR gene accounts for the extra cysteine-binding repeat not found in LDLR. Together, the exons making up the VLDLR gene encode a protein that is 873 amino acid residues long. VLDLR is known to exist as four different protein isoforms: type I, II, III, and IV. These different isoforms result from variations in alternative splicing. The transcript of type I VLDLR (VLDLR-I) is composed of all 19 exons. VLDLR-II, on the other hand, lacks exon 16, which encodes for the O-glycosylation domain between sugar regions. VLDLR-III lacks exon 4 that encodes the third ligand-binding repeat. Finally, VLDLR-IV transcripts lack both exon 16 and exon 4. It has been shown that 75% of VLDLR transcripts exist as isoform type II in mouse brain models. This shows that most VLDLRs in the brain are not glycosylated, as type II lacks exon 16 which encodes the O-glycosylation domain. Isoform type IV is known to be the second most prominent. Evolutionary conservation There is a high level of conservation within the LDL receptor family. In particular, there is 50% overall sequence homology between VLDLR and ApoER2, another lipoprotein receptor of this family. Comparing LDLR and VLDLR, it was found that their primary structures are 55% identical within their ligand-binding regions. The modular structures of these two proteins are almost superimposable, with the only difference being the additional cysteine-rich repeat in VLDLR. This is demonstrated through the alignment of the two receptors according to their linker region; in LDLR, the linker region is located between cysteine-rich repeats four and five of its seven repeats while in VLDLR, the linker region appears to be between repeats five and six of its eight repeats. VLDLR also shows high homology among various species. VLDLR of humans, mice, rats, and rabbits have been identified as 95% identical. Furthermore, there is approximately 84% conservation with the respective protein in chickens. This level of homology between species is much higher than that found for LDLR. Hence, these gene comparisons suggest that VLDLR and LDLR diverged before the LDLRs did among vertebrates. Ligand binding VLDLR binds compounds containing apolipoprotein E (apoE). These ligands attach to the cysteine binding repeats in the N-terminus end. The difference in cysteine-rich repeats between the members of the LDL receptor family lead to the differences in binding affinity. VLDLR, in particular, binds VLDL and intermediate-density lipoprotein (IDL),