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LRP2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

LRP2 gene

The LRP2 gene encodes the megalin protein, a receptor that plays a vital role in transporting substances into cells and regulating various body processes.

Normal Function

The LRP2 gene provides instructions for making a protein called megalin, which functions as a receptor. Receptors have specific sites where other proteins, called ligands, bind to trigger signals that affect cell development and function. Megalin is embedded in the membrane of epithelial cells and is involved in:

  • Absorption of vitamins A and D
  • Immune functioning
  • Stress response
  • Transport of fats in the bloodstream

Megalin is active in the development and function of the central nervous system, eyes, ears, lungs, intestine, reproductive system, and renal tubules in the kidneys.

Health Conditions Related to Genetic Changes

Donnai-Barrow syndrome

Mutations in the LRP2 gene can result in the absence of functional megalin protein. This leads to the excretion of essential ligands in the urine rather than their absorption back into the bloodstream. This condition was previously classified as two separate disorders, with facio-oculo-acoustico-renal (FOAR) syndrome now considered the same as Donnai-Barrow syndrome.

Other disorders

  • Cardiovascular risk: Certain LRP2 polymorphisms are associated with increased levels of low-density lipoproteins (LDLs) and cholesterol, which may increase the risk of cardiovascular disease.
  • Prostate cancer: Genetic variations in LRP2 may influence the progression and severity of prostate cancer. Because androgens (male sex hormones) are ligands for megalin, increased megalin activity may encourage more aggressive tumor growth by allowing tumor cells to absorb more androgens.

Frequently Asked Questions

Hallmark features in infants include severe congenital or early-onset high myopia with progressive retinal thinning, profound sensorineural hearing loss, structural brain malformations (particularly agenesis of the corpus callosum), characteristic facial features such as hypertelorism and downward-slanting eyes, and midline birth defects like diaphragmatic hernia or omphalocele.
Donnai-Barrow syndrome is inherited in an autosomal recessive pattern. When both parents are unaffected heterozygous carriers of an LRP2 pathogenic variant, there is a 25 percent chance with each pregnancy of having an affected child, a 50 percent chance of having an asymptomatic carrier child, and a 25 percent chance of having an unaffected child who inherits two working alleles.
Because megalin is necessary to reclaim vitamin D-binding protein and retinol-binding protein from glomerular filtrate, individuals with LRP2 dysfunction are prone to severe deficiencies in fat-soluble vitamins, particularly vitamins A and D. Patients require routine monitoring of serum 25-hydroxyvitamin D, parathyroid hormone, and vitamin A levels, alongside targeted daily supplementation to prevent complications like rickets, secondary hyperparathyroidism, and progressive visual deterioration.
The megalin protein encoded by LRP2 functions as a multi-ligand endocytic receptor within the brush border of proximal renal tubular epithelial cells, where its primary job is to reclaim filtered nutrients, hormones, and carrier proteins. Loss of megalin causes failure of this reabsorption pathway, resulting in specific proteins (such as vitamin D-binding protein and retinol-binding protein) spilling into the urine, even while the glomerular filtration rate remains functional for an extended period.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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