Low-density lipoprotein receptor-related protein 2 mRNA (LRP2 mRNA)

LRP2 mRNA encodes the low-density lipoprotein receptor-related protein 2, commonly known as megalin, which is a large transmembrane endocytic receptor predominantly expressed in the renal proximal tubule, brain, and other absorptive epithelia. As a therapeutic target, LRP2 mRNA is primarily addressed using RNA-based modalities such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) to modulate the levels of the megalin protein. The encoded protein plays a critical role in the reabsorption of vitamins, hormones, and carrier proteins from the glomerular filtrate, but it also mediates the uptake of nephrotoxic agents like aminoglycosides and cisplatin. Targeting LRP2 mRNA for knockdown is being explored as a strategy to prevent drug-induced kidney injury and to treat certain cancers, such as prostate and breast cancer, where megalin overexpression facilitates the uptake of growth-promoting ligands like androgens. Conversely, loss-of-function mutations in the LRP2 gene result in Donnai-Barrow syndrome, a rare genetic disorder characterized by multi-organ developmental defects and proteinuria. While the megalin protein itself is often used as a delivery vehicle for other kidney-targeted RNA therapeutics, the LRP2 mRNA remains a specific target for silencing in conditions where reducing receptor activity is therapeutically beneficial.

Other names

Megalin mRNAgp330 mRNALRP-2 mRNAGlycoprotein 330 mRNADonnai-Barrow syndrome gene mRNA

RNA interference (siRNA-mediated degradation of mRNA) and antisense inhibition (ASO-mediated knockdown) to reduce the expression of the LRP2/megalin protein.