LRP1 Protein is a protein encoded by the LRP1 gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
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Gene Name
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[LRP1](/genes/lrp1)
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UniProt ID
[Q07954](https://www.uniprot.org/uniprot/Q07954)
PDB Structures
3uali, 5JZW, 6L0J
Molecular Weight
504.6 kDa (precursor)
Subcellular Localization
Cell membrane, endosomes, nucleus
Protein Family
LDL receptor family, LDLR-related proteins
LRP1 (Low Density Lipoprotein Receptor-Related Protein 1), also known as CD91, is a large transmembrane receptor of 4,525 amino acids consisting of:
- Extracellular α chain: Contains 31 ligand-binding complement-type repeats organized in four clusters
- Single transmembrane helix: Spans the plasma membrane
- Cytoplasmic β chain: Contains two NPXY motifs for endocytosis and signaling
- Propeptide: Cleared in the Golgi to form the mature receptor
LRP1 is one of the largest cell surface receptors and functions as a multiligand endocytic receptor 1.
In neurons and glia, LRP1 performs critical functions:
- Aβ clearance: Acts as a major receptor for clearing amyloid-beta from the brain
- Lipid metabolism: Mediates uptake of lipoproteins and cholesterol
- Synaptic plasticity: Regulates NMDA receptor trafficking and synaptic function
- Neuroinflammation: Modulates microglial activation and inflammatory responses
- Protein quality control: Engages the ubiquitin-proteasome system
- Axonal guidance: Controls neuronal migration during development
LRP1 is highly expressed in neurons, astrocytes, and microglia, with particularly high levels in the hippocampus and cortex 2.
- LRP1 mediates Aβ clearance across the blood-brain barrier (BBB)
- Reduced LRP1 expression correlates with impaired Aβ clearance in AD
- Genetic variants in LRP1 affect AD risk
- Loss of LRP1 signaling contributes to synaptic dysfunction
- Therapeutic target for enhancing Aβ clearance 3
- LRP1 can bind α-synuclein and mediate its clearance
- Involved in dopaminergic neuron survival
- May affect LRRK2 pathogenic signaling
- Role in Lewy body formation is under investigation
¶ Stroke and Ischemia
- LRP1 is upregulated after cerebral ischemia
- Mediates post-ischemic inflammation
- Therapeutic potential for stroke intervention
- LRP1 variants associated with hypercholesterolemia
- Role in hepatic and peripheral lipid homeostasis
- LRP1 agonists: Enhancing Aβ clearance (in development)
- Gene therapy: AAV-mediated LRP1 expression
- No FDA-approved LRP1-targeted drugs currently exist
- LRP1: A multiligand receptor in physiology and disease (2012)
- LRP1 in Alzheimer's disease: Role in Aβ clearance (2012)
- LRP1 genetic variants and Alzheimer disease risk (2012)
- LRP1 and amyloid-beta clearance across the blood-brain barrier (2015)