LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman nephritis) and originally named gp330 and subsequently megalin and later LRP2. LRP2/megalin is a multiligand binding receptor found in the plasma membrane of many absorptive epithelial cells. LRP2 is an approximately 600kDa (4665 amino acids) transmembrane glycoprotein with structural similarities to the low density lipoprotein receptor (LDLR). LRP2 has a NPXY motif that is the binding site for Dab2 to initiate clathrin-mediated endocytosis. LRP2 forms a homodimer that changes conformation in response to pH. At pH 7.5 (extracellular pH), LRP2 is considered active, with the leucine loops in an open conformation to allow ligands to bind.[11] At acidic endosomal pHs, the leucine loops collapse to prevent ligands binding.