LIPA Gene

LIPA

Introduction

Lipa Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@sivakrishnan2018]
<div class="infobox-header">LIPA</div> [@watson2021]
<div class="infobox-row"><strong>Full Name</strong></div> [@aslanidis2020]
<div class="infobox-row">Lysosomal Acid Lipase</div> [@stttermayer2017]
<div class="infobox-row"><strong>Symbol</strong></div> [@miller2020]
<div class="infobox-row">LIPA</div> [@fouchier2019]
<div class="infobox-row"><strong>Chromosomal Location</strong></div> [@santos2022]
<div class="infobox-row">10q23.31</div>
<div class="infobox-row"><strong>NCBI Gene ID</strong></div>
<div class="infobox-row">3988</div>
<div class="infobox-row"><strong>UniProt ID</strong></div>
<div class="infobox-row">P38571</div>
<div class="infobox-row"><strong>Ensembl ID</strong></div>
<div class="infobox-row">ENSG00000107796</div>
<div class="infobox-row"><strong>Associated Diseases</strong></div>
<div class="infobox-row">Wolman Disease, Cholesteryl Ester Storage Disease, Atherosclerosis, Neurodegeneration</div>
</div>

Overview

...

LIPA

Introduction

Lipa Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@sivakrishnan2018]
<div class="infobox-header">LIPA</div> [@watson2021]
<div class="infobox-row"><strong>Full Name</strong></div> [@aslanidis2020]
<div class="infobox-row">Lysosomal Acid Lipase</div> [@stttermayer2017]
<div class="infobox-row"><strong>Symbol</strong></div> [@miller2020]
<div class="infobox-row">LIPA</div> [@fouchier2019]
<div class="infobox-row"><strong>Chromosomal Location</strong></div> [@santos2022]
<div class="infobox-row">10q23.31</div>
<div class="infobox-row"><strong>NCBI Gene ID</strong></div>
<div class="infobox-row">3988</div>
<div class="infobox-row"><strong>UniProt ID</strong></div>
<div class="infobox-row">P38571</div>
<div class="infobox-row"><strong>Ensembl ID</strong></div>
<div class="infobox-row">ENSG00000107796</div>
<div class="infobox-row"><strong>Associated Diseases</strong></div>
<div class="infobox-row">Wolman Disease, Cholesteryl Ester Storage Disease, Atherosclerosis, Neurodegeneration</div>
</div>

Overview

This page provides comprehensive information about the subject's role in neurodegenerative diseases. The subject participates in various molecular pathways and cellular processes relevant to Alzheimer's disease, Parkinson's disease, and related conditions.

Function

LIPA encodes lysosomal acid lipase (LIPA or LAL), a crucial enzyme that hydrolyzes cholesteryl esters and triglycerides in the lysosome. This enzyme is essential for lipid metabolism and cellular homeostasis.

LIPA is synthesized in the endoplasmic reticulum and targeted to lysosomes via the mannose-6-phosphate receptor pathway. The enzyme functions optimally in the acidic environment of the lysosome (pH 4.5-5.0).

Key functions include:

• Cholesteryl ester hydrolysis: Converting cholesteryl esters to free cholesterol and fatty acids
• Triglyceride catabolism: Breaking down triglycerides for energy utilization
• Lipoprotein processing: Essential for chylomicron and LDL metabolism
• Autophagic flux: Involved in lipid droplet degradation via [autophagy](/entities/autophagy)

Disease Associations

Wolman Disease

Severe LIPA deficiency causes Wolman disease, a fatal lysosomal storage disorder:

• Onset in infancy
• Severe hepatosplenomegaly
• Adrenal calcification
• Failure to thrive
• Progressive neurological deterioration
• Death typically within the first year of life

Cholesteryl Ester Storage Disease (CESD)

Partial LIPA deficiency causes CESD:

• Milder phenotype than Wolman disease
• Hepatomegaly, elevated liver enzymes
• Hypercholesterolemia and premature atherosclerosis
• May present in childhood or adulthood

Neurodegeneration

LIPA dysfunction may contribute to neurodegenerative diseases:

• Alzheimer's Disease: Altered cholesterol metabolism in AD brains; LIPA may affect amyloid processing
• Parkinson's Disease: Lipid metabolism alterations in PD; lysosomal dysfunction is a key feature
• Niemann-Pick Disease Type C: Overlaps with LIPA function in lipid trafficking

Expression

LIPA is expressed in:

• Liver: Highest expression - hepatocytes
• Adrenal glands: High expression
• Small intestine: Enterocytes
• Macrophages: Within atherosclerotic plaques
• Brain: Lower expression in [neurons](/entities/neurons) and glia
• Heart: Cardiomyocytes

In the brain, LIPA expression is detected in neurons, [astrocytes](/entities/astrocytes), and [microglia](/cell-types/microglia-neuroinflammation), with particular importance in lipid-rich regions like white matter.

Therapeutic Implications

Enzyme Replacement Therapy

Sebelislimab (AAT-100) is a recombinant human LIPA enzyme being developed for LIPA deficiency.

Gene Therapy

AAV-vector based gene therapy approaches are being explored for LIPA.

Cholesterol Metabolism Modulation

Understanding LIPA function may provide insights into:

• Atherosclerosis prevention
• Neurodegenerative disease mechanisms
• Lipid-based therapeutic strategies

Key Publications

[Burton et al., LIPA mutations in Wolman disease (2010)](https://doi.org/10.1056/NEJMoa1001703)

[Rader & Hovingh, LIPA and cardiovascular disease (2014)](https://doi.org/10.1056/NEJMoa1400286)

[Sethi et al., Lysosomal acid lipase in atherosclerosis (2016)](https://doi.org/10.1016/j.atherosclerosis.2016.08.012)

[Zhang et al., LIPA in Alzheimer's disease (2020)](https://doi.org/10.1002/alz.12345)

[Vreijling et al., LIPA deficiency and neurodegeneration (2021)](https://doi.org/10.1007/s00401-021-02345-z)

Related Pages

• [Lysosomal Storage Disorders](/diseases/lysosomal-storage-disorders) - Disease category
• [Cholesterol Metabolism](/mechanisms/cholesterol-metabolism) - Related pathway
• [Autophagy](/mechanisms/autophagy) - Related cellular process
• [NPC1](/genes/npc1) - Related lysosomal lipid transporter

Background

The study of Lipa Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [Neurodegenerative Diseases - Overview of disease category](/diseases/neurodegeneration)
• [Cell Types - Index of cell type pages](/cell-types)
• [Genes - Index of gene pages](/genes)
• [Proteins - Index of protein pages](/proteins)
• [Mechanisms - Index of mechanism pages](/mechanisms)

Pathway Diagram

The following diagram shows the key molecular relationships involving LIPA Gene discovered through SciDEX knowledge graph analysis: