Low-density lipoprotein receptor-related protein 2 (LRP2) and Cubilin (CUBN) complex (LRP2/CUBN)

Megalin (Low-density lipoprotein receptor-related protein 2, LRP2) and Cubilin (CUBN) are large, multiligand endocytic receptors primarily expressed in the apical membrane of renal proximal tubule cells (Christensen et al., 2012). They function as a complex, often alongside the chaperone protein Amnionless (forming the CUBAM complex), to mediate the reabsorption of a wide variety of filtered ligands, including albumin, vitamins (B12 and D), and hormones (Eshbach & Weisz, 2017). This process is essential for maintaining protein and nutrient homeostasis and preventing their loss in urine. Dysfunction or genetic mutations in these receptors lead to conditions such as Donnai-Barrow syndrome and Imerslund-Gräsbeck syndrome, characterized by severe proteinuria and metabolic disturbances (rarediseasesjournal.com). In clinical practice, these receptors are significant as they also mediate the uptake of nephrotoxic drugs like aminoglycosides and polymyxins, contributing to drug-induced kidney injury (Moestrup et al., 1995). Conversely, they are being explored as targets for the delivery of therapeutic agents to the kidney or for blocking the uptake of toxic proteins, such as myeloma light chains, to prevent renal damage (nih.gov). The complex's ability to internalize diverse molecules makes it a critical component of renal physiology and a potential site for therapeutic intervention.

Other names

MegalinCubilingp330gp280LRP2CUBNIntrinsic factor-cobalamin receptorHeymann nephritis antigenCUBAM complex

Receptor-mediated endocytosis