LRP8 (also known as ApoER2 or [apolipoprotein E](/proteins/apoe) receptor 2) is a member of the LDL receptor family that plays crucial roles in synaptic function, Reelin signaling, and neuronal migration. It is particularly important in the central nervous system where it mediates signaling events critical for learning, memory, and neuronal plasticity. LRP8 has been implicated in the pathogenesis of Alzheimer's disease and other neurodegenerative disorders[@herz2006].
Pathway / Mechanism Diagram
Mermaid diagram (expand to render)
Overview
LRP8 (ApoER2) is a transmembrane receptor protein belonging to the LDL receptor superfamily. It is highly expressed in the brain, particularly in the [hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex), and [cerebellum](/brain-regions/cerebellum). LRP8 functions as a receptor for apolipoprotein E (ApoE) isoforms and Reelin, playing essential roles in synaptic plasticity, dendritic spine formation, and neuronal migration during development[@darcangelo1995].
Structure
LRP8 is a type I transmembrane protein with the following structural features:
Domain Architecture
Ligand-binding repeats (LA repeats): Multiple complement-type repeats that bind various ligands including ApoE and Reelin
[Herz J, Chen Y, Reelin, lipoprotein receptors and synaptic plasticity (2006)](https://pubmed.ncbi.nlm.nih.gov/17053810/)
[D'Arcangelo G, Miao GG, Chen SC, et al, A protein related to extracellular matrix proteins deleted in the mouse mutant reeler (1995)](https://pubmed.ncbi.nlm.nih.gov/7715706/)
[Hiesberger T, Trommsdorff M, Howell BW, et al, Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation (1999)](https://pubmed.ncbi.nlm.nih.gov/10571234/)
[Hoe HS, Lee KJ, Carney RS, et al, Engagement of alpha7 nicotinic acetylcholine receptor by endogenous acetylcholine prevents beta-amyloid peptide neurotoxicity (2009)](https://pubmed.ncbi.nlm.nih.gov/19545279/)
[Huang Y, Mucke L, Alzheimer mechanisms and therapeutic strategies (2012)](https://pubmed.ncbi.nlm.nih.gov/22424230/)
[Lane-Donovan C, Philips GT, Herz J, More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration (2014)](https://pubmed.ncbi.nlm.nih.gov/25144875/)