Inherited LRP2 dysfunction in human disease and animal models

Abstract

Gp330/Megalin/Low-Density Lipoprotein Receptor-Related Protein 2 (LRP2) is an endocytic receptor that plays multiple roles in embryonic and adult tissues. It allows the cellular uptake of various bioactive molecules, morphogens, vitamins and hormones. Lack or dysfunction of the receptor affects renal protein reabsorption, lung function, brain and eye development in both man and experimental models. Mutations in LRP2 cause the polymalformative Donnai-Barrow syndrome, a rare autosomal recessive condition, combining developmental delay, facial dysmorphology, hearing defects, high myopia and low-molecular weight proteinuria. We here summarize current knowledge on the receptor action. We particularly focus on the LRP2-associated face and eye anomalies and discuss how the receptor and its interacting proteins, including the multiligand receptor Cubilin (CUBN) may promote health or cause disease.