protein
Acid ceramidase
aka AC, ACDase, Acid CDase
Gene
ASAH1
Organism
Homo sapiens(9606)
Length
395 aa
Mass
44,660 Da
Acid ceramidase (ASAH1, encoded by ASAH1) is a lysosomal hydrolase that catalyzes the breakdown of sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (UniProt: Q13510). The enzyme also catalyzes the reverse synthetic reaction and possesses N-acylethanolamine hydrolase activity. By regulating intracellular levels of ceramides, sphingosine, and sphingosine-1-phosphate—bioactive lipids that mediate cell proliferation, apoptosis, and differentiation—acid ceramidase influences multiple cellular processes. The enzyme is particularly important in epidermal keratinocyte differentiation and may also regulate steroidogenesis through interaction with the nuclear receptor NR5A1 (UniProt: Q13510).
Acid ceramidase deficiency causes Farber lipogranulomatosis, an autosomal recessive lysosomal storage disorder marked by ceramide accumulation, and has been linked to spinal muscular atrophy with progressive myoclonic epilepsy (UniProt: Q13510). Both conditions reflect disrupted sphingolipid homeostasis.
In Alzheimer's disease, acid ceramidase is upregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.93 (Chaparral AD proteomics). This elevation suggests altered ceramide metabolism may contribute to AD pathology, though the functional significance of this change across different brain subcellular compartments remains to be clarified.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+0.928
S3
not detected
Mean log₂FC across detected fractions: +0.9275 (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
Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed:10610716, PubMed:11451951, PubMed:15655246, PubMed:26898341, PubMed:36752535, PubMed:7744740, PubMed:7852294). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:10610716). Has a higher catalytic efficiency towards C12-ceramides versus other ceramides (PubMed:15655246, PubMed:7744740). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed:12764132, PubMed:12815059). For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used (PubMed:12764132). Also has an N-acylethanolamine hydrolase activity (PubMed:15655246). By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes (PubMed:17713573). Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis (By similarity). By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis (PubMed:22261821)
May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity
Disease associations
Farber lipogranulomatosisFRBRL
An autosomal recessive lysosomal storage disorder characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, and marked accumulation of ceramide in lysosomes. Disease severity is variable. The most severe disease subtype is a rare neonatal form with death occurring before 1 year of age.
Spinal muscular atrophy with progressive myoclonic epilepsySMAPME
An autosomal recessive neuromuscular disorder characterized by childhood onset of motor deficits and progressive myoclonic seizures, after normal developmental milestones. Proximal muscle weakness and generalized muscular atrophy are due to degeneration of spinal motor neurons. Myoclonic epilepsy is generally resistant to conventional therapy. The disease course is progressive and leads to respiratory muscle involvement and severe handicap or early death from respiratory insufficiency.
Sources
Last updated 5/8/2026, 6:29:30 AM