Low-density lipoprotein receptor-related protein 1 and Low-density lipoprotein receptor-related protein 6 (LRP1/LRP6)

Low-density lipoprotein receptor-related protein 1 (LRP1) and Low-density lipoprotein receptor-related protein 6 (LRP6) are distinct members of the LDL receptor family that play critical but different roles in human physiology. LRP1, also known as CD91, is a large, multifunctional receptor primarily involved in the endocytosis of over 40 different ligands, including lipoproteins and amyloid-beta, and serves as a signaling modulator in vascular and neuronal health. In contrast, LRP6 is a key co-receptor for the canonical Wnt signaling pathway, where it works alongside LRP5 and Frizzled receptors to activate beta-catenin-dependent gene expression essential for cell proliferation and bone formation. While LRP1 is a major target for drug delivery across the blood-brain barrier and for treating neurodegenerative diseases, LRP6 is a significant focus in oncology and metabolic research due to its role in Wnt-driven tumorigenesis and lipid homeostasis. The designation "LRP1/LRP6" is technically incorrect as a single target because it combines two separate gene products with divergent biological functions and therapeutic applications.

Other names

CD91A2MRAPOERLRP1LRP6ADCAD2STHAG7Alpha-2-macroglobulin receptorApolipoprotein E receptor

LRP1 functions as a multifunctional endocytic receptor and signaling scaffold that clears ligands like amyloid-beta and modulates pathways such as PDGF; LRP6 acts as a critical co-receptor for Wnt ligands, facilitating the stabilization of beta-catenin and subsequent gene transcription.