protein
ATP-binding cassette sub-family A member 2
Gene
ABCA2
Organism
Homo sapiens(9606)
Length
2435 aa
Mass
269,833 Da
ABCA2 (ATP-binding cassette sub-family A member 2) is a lipid transporter that modulates cholesterol sequestration in late endosomes and lysosomes by regulating intracellular sphingolipid metabolism (UniProt: Q9BZC7). The protein facilitates ceramide deacylation and cholesterol homeostasis, and additionally regulates amyloid-beta production through modulation of sphingolipid metabolism and gamma-secretase processing of APP. It may also contribute to myelin formation.
ABCA2 is expressed in the brain and implicated in lipid metabolism pathways critical for neuronal function. UniProt disease associations include intellectual developmental disorder with poor growth and seizures or ataxia (IDPOGSA, MIM 618808), an autosomal recessive condition involving developmental delay and hypotonia (UniProt: Q9BZC7).
In Alzheimer's disease, ABCA2 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC: −0.63, Chaparral AD proteomics). This reduction may impair sphingolipid-mediated cholesterol homeostasis and amyloid-beta regulation, processes central to AD pathogenesis. The downregulation was detected across subcellular fractions in TMT-labeled proteomics analysis.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.626
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.6259 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis (Probable) (PubMed:15238223, PubMed:21810484, PubMed:24201375). May alter the transbilayer distribution of ceramide in the intraluminal membrane lipid bilayer, favoring its retention in the outer leaflet that results in increased acid ceramidase activity in the late endosome/lysosome, facilitating ceramide deacylation to sphingosine leading to the sequestration of free cholesterol in lysosomes (PubMed:24201375). In addition regulates amyloid-beta production either by activating a signaling pathway that regulates amyloid precursor protein transcription through the modulation of sphingolipid metabolism or through its role in gamma-secretase processing of APP (PubMed:22086926, PubMed:26510981). May play a role in myelin formation (By similarity)
Disease associations
Intellectual developmental disorder with poor growth and with or without seizures or ataxiaIDPOGSA
An autosomal recessive disorder characterized by global developmental delay apparent from infancy, impaired intellectual development, hypotonia, and poor overall growth with microcephaly. Additional variable features include dysmorphic features, cataracts, ataxia and seizures.
Sources
Last updated 5/8/2026, 6:39:31 AM