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LDLRAP1 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

LDLRAP1 gene

The LDLRAP1 gene provides instructions for a protein essential to removing cholesterol from the bloodstream by facilitating the transport of LDL receptors into cells.

Normal Function

The LDLRAP1 gene (also known as ARH) provides instructions for making a protein that helps remove cholesterol from the bloodstream. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals. The function of the LDLRAP1 protein is particularly important in the liver, which is the organ responsible for clearing most excess cholesterol from the body.

The LDLRAP1 protein interacts with a protein called a low-density lipoprotein receptor. This type of receptor attaches (binds) to particles called low-density lipoproteins (LDLs), which are the primary carriers of cholesterol in the blood. The receptors sit on the outer surface of cells, where they pick up LDLs circulating in the bloodstream. The LDLRAP1 protein appears to play a critical role in moving these receptors, together with their attached LDLs, from the cell surface to the interior of the cell. Once inside the cell, LDLs are broken down to release cholesterol. The cholesterol is then used by the cell, stored, or removed from the body.

Health Conditions Related to Genetic Changes

Familial hypercholesterolemia

More than 20 mutations in the LDLRAP1 gene have been shown to cause a form of familial hypercholesterolemia called autosomal recessive hypercholesterolemia. These mutations lead to the production of an abnormally small, nonfunctional version of the LDLRAP1 protein or prevent cells from making any of this protein. Without the LDLRAP1 protein, low-density lipoprotein receptors are unable to remove LDLs from the bloodstream effectively. Although the receptors can still bind normally to LDLs, these molecules are not properly transported into cells (particularly liver cells). As a result, many extra LDLs remain in the blood.

Because LDLs are major carriers of cholesterol in the blood, people with mutations in the LDLRAP1 gene have very high blood levels of cholesterol. As the excess cholesterol circulates through the bloodstream, it is deposited abnormally in tissues such as the skin, tendons, and arteries that supply blood to the heart (coronary arteries). A buildup of cholesterol in the walls of coronary arteries greatly increases a person's risk of having a heart attack.

Other Names for This Gene

  • ARH
  • ARH_HUMAN
  • autosomal recessive hypercholesterolemia protein
  • FHCB1
  • FHCB2
  • LDL receptor adaptor protein
  • MGC34705

Frequently Asked Questions

RH typically presents with very high LDL cholesterol levels, tendon xanthomas, and early cardiovascular disease, but the LDL receptors themselves are functional. The defect lies in the adaptor protein that mediates receptor internalization, so LDL binding is normal but clearance is impaired. Genetic testing for LDLRAP1 is needed when LDLR mutations are absent but clinical features suggest FH.
Confirmation requires sequencing of the LDLRAP1 gene from a blood sample. The test looks for pathogenic variants that produce a truncated or nonfunctional protein. It is usually ordered by a lipid specialist or geneticist when a patient has severe hypercholesterolemia unexplained by lifestyle or other causes.
Treatment focuses on aggressive LDL‑lowering therapy: high‑dose statins, ezetimibe, and possibly PCSK9 inhibitors or lipoprotein apheresis if LDL levels remain above target. Lifestyle changes—low saturated fat, regular exercise, and weight management—are also essential. Regular monitoring of lipid panels and cardiovascular risk is required.
Currently, no approved gene therapy exists for ARH. Research is ongoing into gene editing and novel pharmacologic agents that could restore LDLRAP1 function or bypass the internalization step. Patients should stay informed about clinical trials and discuss eligibility with their lipid specialist.
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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