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

PSAP gene

The PSAP gene provides instructions for making prosaposin, a precursor protein that is broken down into saposins necessary for the recycling of fatty substances in cells.

Normal Function

The PSAP gene provides instructions for making a protein called prosaposin. This protein is involved in a number of biological functions, including the development of the nervous system and the reproductive system. Prosaposin is the precursor of four smaller proteins called saposin A, B, C, and D, which are produced when prosaposin is broken up (cleaved).

The individual saposins are found in cellular structures called lysosomes, which are the cell's recycling centers. The saposins help lysosomal enzymes break down fatty substances called sphingolipids.

The saposin B protein works with several enzymes to break down sphingolipids. Its most critical biological role seems to be associated with the enzyme arylsulfatase A. This enzyme is involved in breaking down a subgroup of sphingolipids called sulfatides, especially in the nervous system's white matter, which consists of nerve fibers covered by myelin. Myelin is a substance that insulates and protects nerves. The saposin C protein works with the enzyme beta-glucocerebrosidase to break down another sphingolipid called glucocerebroside. Saposins A and D are also involved in processing sphingolipids.

Health Conditions Related to Genetic Changes

Metachromatic leukodystrophy

In a small number of individuals with metachromatic leukodystrophy, a disorder that causes deterioration of nervous system functions, researchers have identified PSAP gene mutations that result in a shortage (deficiency) of the saposin B protein. This deficiency interferes with the breakdown of sulfatides, which can accumulate to toxic levels in the nervous system. The buildup of sulfatides gradually destroys myelin, leading to a loss of white matter (leukodystrophy) and impairment of nervous system function.

Other disorders

In a few individuals, mutations in the PSAP gene interfere with the function of the saposin C protein, resulting in a disorder that resembles a severe form of Gaucher disease. Signs and symptoms include neurological problems and abnormal enlargement of the liver and spleen (hepatosplenomegaly). A few PSAP gene mutations have also been identified in individuals with signs and symptoms resembling another leukodystrophy called Krabbe disease.

In addition, a few mutations in the PSAP gene have been identified that prevent the production of more than one of the saposin proteins. Individuals with these mutations have massive accumulation of sphingolipids in their nervous system and other organs, resulting in very severe neurological disease, respiratory problems, and hepatosplenomegaly.

Other Names for This Gene

  • Prosaposin (sphingolipid activator protein-1)
  • prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy)
  • prosaptides
  • SAP1
  • SAP2 (sphingolipid activator protein-2)
  • SAP_HUMAN
  • SGP-1 (sulfoglycoprotein-1)

Frequently Asked Questions

While the vast majority of metachromatic leukodystrophy cases are caused by mutations in the ARSA gene, which directly affects the arylsulfatase A enzyme, PSAP mutations cause a secondary deficiency. In PSAP-related cases, the arylsulfatase A enzyme itself is present but lacks the necessary saposin B cofactor to function properly. This distinction is critical for diagnosis because standard enzyme activity tests may show normal arylsulfatase A levels in the blood if the test does not specifically account for the missing cofactor, potentially leading to a missed diagnosis if only ARSA is tested.
Current enzyme replacement therapies for metachromatic leukodystrophy, such as idursulfase beta, target the arylsulfatase A enzyme. Since PSAP mutations result in a lack of the saposin B cofactor rather than a lack of the enzyme itself, standard enzyme replacement may not be effective unless the therapy includes the necessary cofactor or is combined with gene therapy that restores saposin B production. Research is ongoing into gene therapy approaches that could correct the underlying PSAP mutation to restore saposin B levels and allow the existing arylsulfatase A enzyme to function correctly.
Clinically, the symptoms of PSAP-related metachromatic leukodystrophy are often indistinguishable from ARSA-related forms, including progressive motor and cognitive decline, spasticity, and loss of myelin. However, because PSAP mutations are rare, they are typically considered when a patient presents with classic leukodystrophy symptoms but has normal or near-normal arylsulfatase A enzyme activity in standard laboratory assays. Genetic sequencing of the PSAP gene is then required to identify the specific mutation affecting saposin B production.
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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