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Target intelligence / Profile preview
Low-density lipoprotein receptor-related protein 1 (LRP1) - Cluster IV (LRP1)
- Target
- LRP1
- Molecular classification
- Receptor, Low-density lipoprotein receptor family, Scavenger receptor
01
Overview
Low-density lipoprotein receptor-related protein 1 (LRP1) is a massive, multifunctional scavenger receptor and signaling molecule belonging to the LDL receptor family (UniProt P98157). It is composed of a 515 kDa extracellular alpha chain and an 85 kDa transmembrane beta chain. The alpha chain contains four distinct ligand-binding domains, known as Clusters I through IV, with Cluster IV (comprising complement-type repeats 31–41) being a major site for ligand interaction, including alpha-2-macroglobulin and various blood-clotting factors (PMID: 17430443). LRP1 is essential for the clearance of amyloid-beta from the brain, and its dysfunction is heavily implicated in the pathogenesis of Alzheimer's disease (PMID: 23839367). In oncology, LRP1 modulates the tumor microenvironment by regulating protease activity and growth factor signaling. Due to its high efficiency in receptor-mediated transcytosis, Cluster IV is a primary target for drug delivery systems designed to cross the blood-brain barrier, such as the peptide Angiopep-2 (PMID: 18495744).
- Other names
- CD91Alpha-2-macroglobulin receptorA2MRAPOERLRP1 Cluster 4Prolow-density lipoprotein receptor-related protein 1
02
Mechanism of action
Receptor-mediated transcytosis for blood-brain barrier crossing and receptor-mediated endocytosis for ligand sequestration (PMID: 18495744).
03
Biological functions
EndocytosisReceptor-mediated transcytosis (PMID: 18495744)Signal transductionProtease clearanceLipid metabolismAmyloid-beta clearance (PMID: 23839367)
04
Disease associations
Alzheimer's diseaseCancer (metastasis and progression)Cardiovascular diseaseAtherosclerosisCoagulopathy
05
Safety considerations
Ubiquitous expression leading to potential systemic off-target effects (UniProt P98157)Interference with homeostatic protein clearance, such as clotting factors (PMID: 17430443)Potential for altered lipid metabolism
06
Interacting drugs
Angiopep-2 (ANG1005)
3 more in the full profile.
07
Biomarkers
Soluble LRP1 (sLRP1) levels in plasma or cerebrospinal fluid (PMID: 23839367)LRP1 expression levels in tumor biopsies (PMID: 28652343)
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