Low-density lipoprotein receptor-related protein 1 (CD91) (LRP1)

Low-density lipoprotein receptor-related protein 1 (LRP1), commonly known as CD91, serves as the primary receptor for the heat shock protein gp96 (GRP94) on the surface of antigen-presenting cells such as dendritic cells and macrophages [1, 2]. In its role as an immune chaperone receptor, CD91 binds to extracellular gp96-peptide complexes that are released during cellular necrosis or stress [4]. This binding event triggers receptor-mediated endocytosis, allowing the chaperoned peptides to be internalized and subsequently cross-presented on MHC class I molecules to activate CD8+ cytotoxic T lymphocytes [2, 4]. This pathway is a critical link between innate and adaptive immunity, particularly in the context of anti-tumor immune surveillance. Beyond immunology, LRP1 is a multifunctional scavenger receptor involved in the clearance of diverse ligands, including alpha-2-macroglobulin and amyloid-beta, and it plays a role in maintaining the integrity of the blood-brain barrier [3]. Therapeutic strategies targeting this receptor include gp96-based autologous vaccines like Vitespen, which aim to harness the cross-presentation pathway to treat cancers such as renal cell carcinoma and glioma [5]. Additionally, LRP1 is being explored as a target for drug delivery systems designed to transport therapeutic agents across the blood-brain barrier via transcytosis.

Other names

CD91LRP1Alpha-2-macroglobulin receptorA2MRApolipoprotein E receptorAPOERHeat shock protein gp96 receptor

Facilitates the uptake and cross-presentation of chaperoned peptides to MHC class I molecules on antigen-presenting cells, thereby priming cytotoxic T-cell responses; also mediates transcytosis for drug delivery across the blood-brain barrier.