Low density lipoprotein receptor-related protein 2 (LRP2)

Low density lipoprotein receptor-related protein 2 (LRP2), also known as megalin or gp330, is a giant transmembrane glycoprotein (~600 kDa) of the LDL receptor family[1][8]. It is predominantly expressed in the apical membrane of epithelial cells in the kidney proximal tubule, as well as in the thyroid, brain ependyma, and several other tissues[1][3][7]. LRP2 functions as a multi-ligand endocytic receptor, binding and internalizing a broad range of ligands, including vitamin-binding proteins, hormones (such as thyroglobulin), lipoproteins, and signaling molecules. This receptor is critical for homeostatic uptake of proteins and regulation of signaling pathways such as sonic hedgehog and BMP4, with vital roles in kidney function, neurogenesis, brain and craniofacial development[3][6][7]. Pathogenic variants in LRP2 cause developmental syndromes with neurological, craniofacial, and renal involvement (e.g., Donnai-Barrow syndrome). Dysregulation or mutations can contribute to disease via defective uptake in the kidney (proteinuria), abnormal cholesterol metabolism, or impaired neurodevelopment[5][7]. LRP2 can be targeted experimentally (e.g., by RAP) but is not currently a direct target of therapeutic drugs.

Other names

Megalingp330LRP-2

Ligand endocytosis (Lysosomal trafficking and clearance); Receptor-mediated uptake and clearance of proteins/vitamins; Modulation of SHH signaling via complex internalization; BMP4 clearance via endocytic removal