Low-density lipoprotein receptor-related protein 1 (LRP1) - Cluster II (LRP1 Cluster II)

Low-density lipoprotein receptor-related protein 1 (LRP1) is a massive, multifunctional scavenger and signaling receptor 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. Cluster II is the largest of the four ligand-binding domains within the alpha chain and is responsible for interacting with the majority of LRP1's 40+ known ligands, including alpha-2-macroglobulin and apolipoprotein E (PubMed: 10542246). In the central nervous system, LRP1 Cluster II is a major mediator of amyloid-beta clearance across the blood-brain barrier, making it a focal point for Alzheimer's disease research (PubMed: 18448642). Furthermore, its high endocytic capacity is frequently exploited in pharmacology to facilitate the delivery of therapeutic agents into the brain using peptide-based Trojan horse strategies like Angiopep-2 (PubMed: 18448642). Dysregulation of LRP1 is also implicated in atherosclerosis and tumor progression due to its roles in lipid metabolism and cell signaling (PubMed: 21903031).

Other names

CD91Alpha-2-macroglobulin receptorA2MRApolipoprotein E receptorAPOERLRP1-alpha chain Cluster II

Ligand binding to Cluster II triggers receptor-mediated endocytosis, facilitating the internalization of ligands for lysosomal degradation or transcytosis across the blood-brain barrier; it also initiates intracellular signaling cascades such as the MAPK, PI3K, and Shp2 pathways (PubMed: 10542246, PubMed: 18448642).