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

Low-density lipoprotein receptor-related protein 1 (LRP1), also known as CD91 or alpha-2-macroglobulin receptor, is a large, multifunctional transmembrane protein that serves as a primary mediator of extracellular matrix (ECM) component clearance. It is highly expressed in tissues such as the liver and brain, where it functions as a scavenger receptor to internalize and degrade diverse ligands, including collagen, thrombospondin, and beta-amyloid, through the endocytic-lysosomal pathway [1, 4, 10]. Beyond its role in clearance, LRP1 acts as a vital signaling hub by interacting with co-receptors and adaptor proteins to regulate cell migration, survival, and tissue remodeling [10, 15]. In pathological contexts, LRP1 is essential for the clearance of amyloid-beta in Alzheimer's disease and is frequently dysregulated in cancer and atherosclerosis, where it influences tumor invasion and vascular stability [4, 15]. While LRP1 is the most broad-spectrum receptor in this category, other specialized receptors like C-type mannose receptor 2 (uPARAP/Endo180) are also involved in specific ECM clearance pathways and are being investigated as therapeutic targets, particularly through antibody-drug conjugates [5, 8, 11].

Other names

Alpha-2-macroglobulin receptorA2MRCD91Apolipoprotein E receptorAPOERCluster of differentiation 91Extracellular matrix component clearance receptor

Mediates the receptor-mediated endocytosis and lysosomal degradation of a wide array of extracellular ligands including collagen, amyloid-beta, and protease-inhibitor complexes; functions as a signaling scaffold for intracellular pathways.