Sphingomyelin phosphodiesterase · UniProt P17405
SMPD1 encodes lysosomal acid sphingomyelinase (ASM), a phosphodiesterase that hydrolyzes sphingomyelin to ceramide and phosphocholine, functioning as a central regulator of sphingolipid metabolism with broad roles in membrane dynamics, cell death signaling, autophagy, immune regulation, and vascular homeostasis. ASM is activated by caspase-7 cleavage to generate ceramide for plasma membrane repair following gasdermin D and perforin pore formation, a mechanism essential for epithelial cell extrusion during infection and for cytotoxic lymphocyte-mediated bacterial clearance (PMID:35705808). The ceramide produced by ASM organizes membrane raft signaling platforms that mediate Fas-induced apoptosis via GD3 accumulation (PMID:9500792), NLRP3 inflammasome activation through a CD36/NF-κB/TXNIP axis (PMID:33612104), TRAIL-induced NADPH oxidase-dependent redox signaling (PMID:23108456), and blood–brain barrier regulation via PP1-mediated ERM dephosphorylation and caveolae-cytoskeleton uncoupling (PMID:30269989). Loss-of-function mutations in SMPD1 cause Niemann-Pick disease types A and B, with disease severity modulated by paternal imprinting that results in preferential maternal allele expression (PMID:16642440, PMID:18815062).
Chromosomal mapping placed SMPD1 at 11p15.1–p15.4, establishing its genomic location and setting the stage for linkage to Niemann-Pick disease loci in this region.
Evidence Somatic cell hybrid PCR and in situ hybridization
Cloning of SMPD1 defined its six-exon gene structure and confirmed it encodes acid sphingomyelinase, the enzyme that hydrolyzes sphingomyelin to ceramide and phosphocholine, establishing the molecular identity underlying Niemann-Pick disease.
Evidence Genomic cloning and nucleotide sequencing with exon/intron junction analysis
Demonstration that ASM is required for Fas-triggered GD3 ganglioside accumulation and apoptosis established ceramide generation as a signaling output, not merely a catabolic step, linking SMPD1 to receptor-mediated cell death.
Evidence NPD patient lymphoblasts lacking ASM showed impaired Fas-induced apoptosis; mannose receptor-mediated ASM transfer and exogenous ceramide rescued the phenotype
Discovery of paternal imprinting of SMPD1 revealed an epigenetic layer of regulation: differential promoter methylation causes preferential maternal allele expression, explaining variable residual ASM activity and disease severity among Niemann-Pick patients with identical genotypes.
Evidence Allele-specific RT-PCR, bisulfite sequencing, and 5-aza-2'-deoxycytidine demethylation rescue
Structure–function analysis of NPD-causing mutations (L302P, H421Y, R496L, ΔR608) showed that these variants abolish catalytic activity without preventing lysosomal trafficking, separating the protein folding/sorting pathway from enzymatic function.
Evidence In vitro/in situ enzyme assays, Western blotting, fluorescent microscopy, co-IP with BiP, 3D modeling in transfected cells and knock-in mice
TRAIL-induced ASM translocation to the plasma membrane and ceramide-dependent clustering of NADPH oxidase in membrane rafts revealed that ASM-generated ceramide reorganizes signaling platforms to produce superoxide in endothelial cells, extending ASM's role to redox signaling.
Evidence Confocal and FRET imaging, superoxide measurement in Smpd1+/+ vs. Smpd1−/− endothelial cells, vasodilation assays
Two studies expanded ASM's downstream biology: ASM-derived ceramide suppresses Treg induction via AKT/Rictor signaling, and controls autophagosome trafficking through lysosomal TRPML1-Ca²⁺/dynein, connecting SMPD1 to adaptive immunity and autophagy maturation.
Evidence Smpd1−/− splenocytes with ceramide rescue for Treg; lysosomal Ca²⁺ imaging and TRPML1 manipulation in Smpd1−/− coronary smooth muscle cells for autophagy
Identification of EGR1/EGR3 as direct transcriptional activators of the SMPD1 promoter provided the first defined transcription factor–promoter interaction for ASM expression, showing how external stimuli (resveratrol) increase ASM activity.
Evidence EMSA, ChIP, and promoter-reporter assays in leukemia and cancer cells
ASM was shown to maintain blood–brain barrier integrity by restraining caveolae-mediated transcytosis: excess ASM in aged brain endothelium activates PP1, dephosphorylates ERM proteins, uncouples caveolae from the cytoskeleton, and increases BBB permeability, establishing a ceramide-driven mechanism of age-related neurovascular decline.
Evidence Endothelial-specific Smpd1 KO and overexpression in mice, ERM phosphorylation assays, caveolae imaging, BBB permeability and cognitive testing
SMPD1 knockout increases α-synuclein levels, and certain NPD mutations (L302P, fsP330) impair ASM lysosomal trafficking rather than only catalytic activity, linking ASM loss to Parkinson's disease-relevant protein accumulation and refining the genotype–phenotype spectrum.
Evidence CRISPR/Cas9 KO and siRNA KD in HeLa and dopaminergic BE(2)-M17 cells, immunofluorescence for localization, α-synuclein immunoblotting
The saposin domain was shown to be essential for catalytic function: the C133Y mutation in this domain abolishes activity despite normal expression and lysosomal localization, defining a critical structural requirement beyond the catalytic center.
Evidence Patient fibroblasts and COS-7 transient expression of C133Y mutant with subcellular localization and enzyme activity assays
Sortilin was identified as the receptor that mediates ASM trafficking from the trans-Golgi network to lysosomes; sortilin knockdown in brain reduces ASM/ceramide signaling and downstream RhoA/ROCK2-dependent dendritic spine remodeling, linking ASM trafficking to synaptic plasticity.
Evidence Sortilin KD/OE in mouse prefrontal cortex and hippocampus, ASM inhibitor rescue, RhoA/ROCK2 activity assays, dendritic spine imaging in a CUMS depression model
A ceramide–TFEB positive feedback loop was delineated in trophoblasts: ceramide drives TFEB nuclear translocation, TFEB directly activates SMPD1 transcription, and lysosomal exocytosis translocates ASM to the cell surface, implicating this circuit in preeclampsia pathogenesis.
Evidence ChIP and reporter assays for TFEB–SMPD1 promoter binding, exosome isolation, endothelial functional assays, SMPD1 inhibitor rescue
The discovery that caspase-7 cleaves and activates ASM to generate ceramide for membrane repair after gasdermin D and perforin pore formation unified ASM's roles in innate immunity, cytotoxic lymphocyte killing, and epithelial homeostasis, establishing a direct biochemical activation mechanism.
Evidence Caspase-7-deficient mice, intestinal organoids, multiple in vivo infection models (Salmonella, C. violaceum, L. monocytogenes), biochemical cleavage assays, ceramide quantification, membrane repair assays
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 1992 | SMPD1 encodes acid sphingomyelinase (ASM), a lysosomal phosphodiesterase that hydrolyzes sphingomyelin to ceramide and phosphocholine. The gene contains six exons and five introns, with exon 2 encoding ~44% of the mature polypeptide. Alternative splicing of exon 3 generates multiple transcript isoforms. | Genomic cloning, nucleotide sequencing, exon/intron junction analysis | Genomics | High | 1740330 |
| 1991 | The SMPD1 gene was localized to chromosomal region 11p15.1–p15.4 by PCR analysis of somatic cell hybrids and confirmed by in situ hybridization. | Somatic cell hybrid PCR concordance analysis and in situ hybridization | Genomics | High | 2004772 |
| 1998 | Acidic sphingomyelinase (ASM, encoded by SMPD1) is required for Fas-induced GD3 ganglioside accumulation and efficient apoptosis in lymphoid cells. NPD lymphoblasts lacking ASM activity fail to activate ASM after Fas cross-linking, fail to accumulate GD3, and show impaired apoptosis; mannose receptor-mediated transfer of ASM rescues GD3 accumulation and rapid apoptosis. | Patient-derived NPD lymphoblast cell lines (loss-of-function genetic model), exogenous ceramide rescue, mannose receptor-mediated ASM transfer, GD3 accumulation assay | The Journal of experimental medicine | High | 9500792 |
| 2006 | SMPD1 is paternally imprinted; differential methylation of CpG dinucleotides in the SMPD1 promoter results in preferential maternal allele expression, influencing residual ASM activity and disease severity in Niemann-Pick disease. | Genomic sequencing vs. RT-PCR allele discrimination, 5-aza-2'-deoxycytidine demethylation treatment, bisulfite genomic sequencing of SMPD1 promoter | American journal of human genetics | High | 16642440 |
| 2008 | Common NPD-causing SMPD1 mutations (L302P, H421Y, R496L, ΔR608) abolish ASM catalytic activity without preventing protein expression or lysosomal trafficking; mutant ASM polypeptides are expressed at normal levels and reach lysosomes but are enzymatically inactive. Co-immunoprecipitation with ER chaperone BiP confirmed proper folding attempts. | In vitro and in situ enzyme assays, Western blotting, fluorescent microscopy, co-immunoprecipitation with BiP, 3D structural modeling, reticulocyte lysate expression, transgenic knock-in mice | Molecular genetics and metabolism | High | 18815062 |
| 2012 | TRAIL activates ASM in coronary arterial endothelial cells, causing ASM translocation to the plasma membrane, ceramide production, and NADPH oxidase aggregation in membrane raft clusters, thereby generating redox signaling platforms that impair endothelial function. SMPD1-knockout cells show absence of lysosome–membrane fusion and membrane raft clustering after TRAIL stimulation. | Confocal microscopy, FRET imaging of lysosome–membrane raft co-trafficking, NADPH oxidase superoxide measurement, comparison of Smpd1+/+ vs. Smpd1−/− endothelial cells, vasodilation assays | Journal of molecular medicine | High | 23108456 |
| 2016 | ASM (SMPD1) is a negative regulator of regulatory T cell (Treg) development. ASM-deficient mice have higher numbers of Tregs; in vitro induction with TGF-β and IL-2 produces more Foxp3+ iTregs in ASM-deficient T cells, associated with reduced AKT (Ser473) phosphorylation and lower Rictor levels. Exogenous ceramide (C6) reduces iTreg numbers in both ASM-deficient and WT cells. | Flow cytometry on Smpd1−/− splenocytes and isolated naive T cells, in vitro Treg induction, CFSE proliferation assay, Western blotting, qRT-PCR, ceramide rescue experiment | Cellular physiology and biochemistry | Medium | 27512981 |
| 2016 | ASM (SMPD1) controls autophagosome trafficking by regulating lysosomal TRPML1 channel-mediated Ca²⁺ release, which in turn activates dynein motor activity required for autophagosome–lysosome fusion in coronary arterial smooth muscle cells. | Lysosomal Ca²⁺ imaging, dynein activity assay, TRPML1 gene silencing/overexpression, autophagosome trafficking imaging in Smpd1−/− vs. Smpd1+/+ CASMCs | Frontiers in bioscience (Landmark edition) | Medium | 26709800 |
| 2018 | ASM (Smpd1) controls autophagy maturation in vascular smooth muscle cells. PDGF-BB stimulation in Smpd1−/− SMCs causes prolonged Akt activation, reduced autophagosome biogenesis, p62/SQSTM1 accumulation, and a myofibroblast-like phenotypic transition; Akt inhibition or p62 silencing rescues this phenotype. | Smpd1−/− primary SMC cultures, Western blotting, immunofluorescence, Akt inhibitor, siRNA silencing of p62, cytokine/adhesion molecule measurement | Cell death & disease | Medium | 30451833 |
| 2018 | ASM (SMPD1) is a critical regulator of brain endothelial barrier integrity. Increased ASM in aged brain endothelium promotes caveolae-mediated transcytosis and blood-brain barrier (BBB) disruption via protein phosphatase 1-mediated dephosphorylation of ERM (ezrin/radixin/moesin) proteins, reducing caveolae-cytoskeleton interaction; genetic inhibition or endothelial-specific knockdown of ASM reduces BBB breakdown and neurocognitive impairment in aged mice. | Endothelial-specific Smpd1 knockout and overexpression in mice, primary brain endothelial cell culture, caveolae imaging, ERM phosphorylation assays, BBB permeability measurement, cognitive testing | Neuron | High | 30269989 |
| 2019 | The SMPD1 p.L302P and p.fsP330 mutations impair trafficking of ASM protein to the lysosome. SMPD1 knockout and knockdown in HeLa and dopaminergic BE(2)-M17 cells result in increased α-synuclein levels, suggesting ASM activity promotes α-synuclein clearance. | CRISPR/Cas9 knockout and siRNA knockdown of SMPD1, lysosomal localization assays (immunofluorescence), α-synuclein immunoblotting, mass spectrometry-based ASM activity assay | Movement disorders | Medium | 30788890 |
| 2019 | Lysosomal ceramide derived from ASM (Smpd1) drives phenotypic switching of vascular smooth muscle cells (VSCs) and small extracellular vesicle (sEV) secretion, contributing to arterial medial calcification. Smooth muscle-specific Smpd1 overexpression reduces lysosome-MVB interaction and increases sEV release; the ASM inhibitor amitriptyline prevents these effects. | Smpd1 smooth-muscle-specific transgenic mice (Smpd1trg/SMcre), Vitamin D-induced calcification model, immunofluorescence (CD63, AnX2, ALP, LAMP1, VPS16), amitriptyline pharmacological inhibition, calcium deposition assay in CASMCs | Journal of cellular and molecular medicine | Medium | 31743567 |
| 2020 | Homozygous Smpd1 deficiency (ASM loss) aggravates brain ischemia/reperfusion injury by increasing ICAM-1 on cerebral microvessels and enhancing polymorphonuclear neutrophil (PMN) infiltration into the brain, while heterozygous deficiency is protective against mild focal ischemia. PMN depletion abrogated the increased injury in Smpd1−/− mice. | Smpd1+/+, Smpd1+/−, Smpd1−/− mice; middle cerebral artery occlusion (MCAO) model; BBB permeability measurement; leukocyte/PMN quantification; anti-Ly6G PMN depletion | Basic research in cardiology | Medium | 33057972 |
| 2021 | Ceramide accumulation in preeclamptic trophoblasts drives TFEB nuclear translocation and lysosomal biogenesis; TFEB directly regulates SMPD1 expression, creating a positive feedback loop. Ceramide-induced lysosomal exocytosis translocates SMPD1 to the apical syncytiotrophoblast membrane and releases active SMPD1 via ceramide-enriched exosomes, which impair endothelial tubule formation and cause endothelial activation. | In vitro and in vivo ceramide treatment, TFEB localization imaging, ChIP/reporter assay for TFEB–SMPD1 promoter binding, exosome isolation, endothelial cell functional assays, SMPD1 inhibitor rescue | Frontiers in cell and developmental biology | Medium | 34017832 |
| 2022 | Caspase-7 cleaves and activates ASM (SMPD1), which generates ceramide to enable membrane repair after gasdermin D pore formation, counteracting pore-driven lysis. This mechanism is required for intestinal epithelial cell extrusion during Salmonella infection (in organoids and mice) and for clearance of bacterial infections after perforin pore attack by NK cells and CTLs in hepatocytes. Caspase-7-deficient cells cannot complete extrusion or apoptosis, and ASM cleavage is the mechanistic link. | Caspase-7-deficient mouse models, intestinal organoids, in vivo infection models (S. Typhimurium, C. violaceum, L. monocytogenes), biochemical cleavage assays, ceramide quantification, membrane repair assays | Nature | High | 35705808 |
| 2016 | Resveratrol increases SMPD1 mRNA and ASM enzymatic activity in leukemia and cancer cells through transcriptional upregulation by EGR1 and EGR3 transcription factors, which directly bind the SMPD1 promoter, leading to ceramide accumulation and reduced sphingomyelin. | ASM activity assay, RT-PCR, sphingolipid measurements, transcription factor overexpression with SMPD1 promoter reporter assay, EMSA, ChIP assay | Biochemical and biophysical research communications | Medium | 26809095 |
| 2021 | Sortilin facilitates trafficking of ASM from the trans-Golgi network to the lysosome. Sortilin knockdown in mouse prefrontal cortex and hippocampus reduces ASM/ceramide signaling, which decreases RhoA/ROCK2 activation and dendritic spine remodeling, ameliorating depressive-like behaviors. | Sortilin knockdown/overexpression in vivo (CUMS mouse model), ASM inhibitor (SR33557) injection, ceramide level measurement, RhoA/ROCK2 activity assay, dendritic spine imaging | Acta pharmacologica Sinica | Medium | 34931016 |
| 2020 | Decreased SMPD1 activity in bronchial airway epithelial cells causes pro-oxidative stress, NRF2 activation, increased cytokine production (IL-8, GRO-α, GM-CSF, CCL20), and enhanced neutrophil recruitment, even without infection. Expression of catalytically inactive SMPD1[L225P] but not wild-type ASM activates NRF2, indicating the effect is activity-dependent. | Inducible shRNA knockdown of SMPD1 in BEAS-2B cells, NRF2 reporter assay, cytokine ELISA/qPCR, neutrophil chemotaxis assay, catalytically inactive mutant overexpression | Biochemical and biophysical research communications | Medium | 27865842 |
| 2021 | ASM (SMPD1) activity promotes NLRP3 inflammasome activation through a ceramide/CD36/NF-κB/TXNIP signaling axis in macrophages. ASM inhibition by imipramine suppresses LPS/ATP-induced ceramide accumulation and NLRP3/caspase-1/IL-1β/IL-18 expression; exogenous ceramide activates the inflammasome via CD36-dependent NF-κB activation of TXNIP. | ASM activity assay, immunofluorescence, Western blotting, RT-PCR, ELISA, siRNA against TXNIP, CD36 inhibitor (SSO), NF-κB inhibitor (SN50), verapamil (TXNIP inhibitor), imipramine (ASM inhibitor) | Lipids in health and disease | Medium | 33612104 |
| 2020 | SMPD1 knockdown and knockout result in reduced ceramide, increased sphingomyelin, and 5-FU resistance in colorectal cancer cells, with siRNA-SMPD1 treatment of sensitive DLD-1 cells phenocopying the resistant state. | MALDI-MS and LC-MRM-MS lipidomics, siRNA knockdown of SMPD1, drug resistance functional assay | Scientific reports | Medium | 32273521 |
| 2024 | Structure-based molecular dynamics simulations of ASM in a lysosomal membrane environment, combined with pathogenicity predictions, identified that SMPD1 missense variants exert pathogenic effects through destabilization of protein structure or through local and long-range effects at catalytic, zinc-binding, and substrate-binding functional sites; predictions were validated against experimental residual activity data for 135 variants. | Molecular dynamics simulation in lysosomal membrane, pathogenicity prediction tools, validation against experimental ASM activity data for 135 variants | Biochimica et biophysica acta. Molecular basis of disease | Low | 38782304 |
| 2020 | The SMPD1 p.C133Y mutation in the N-terminal saposin domain completely abolishes ASM catalytic activity despite normal protein expression and proper lysosomal localization, demonstrating that the three-dimensional structure of the saposin domain is essential for catalytic activity. | Patient fibroblast immunoblotting, COS-7 cell transient expression of mutant ASM, subcellular localization by immunofluorescence, enzyme activity assay | The Tohoku journal of experimental medicine | Medium | 31941852 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2002 | Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. | Journal of the American Academy of Dermatology | 261 | 11907497 |
| 1999 | A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. | The British journal of dermatology | 200 | 10468798 |
| 2013 | The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease. | Neurology | 152 | 23535491 |
| 1998 | Acidic sphingomyelinase (ASM) is necessary for fas-induced GD3 ganglioside accumulation and efficient apoptosis of lymphoid cells. | The Journal of experimental medicine | 133 | 9500792 |
| 2021 | SVIM-asm: structural variant detection from haploid and diploid genome assemblies. | Bioinformatics (Oxford, England) | 124 | 33346817 |
| 1992 | Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1). | Genomics | 111 | 1740330 |
| 2022 | Caspase-7 activates ASM to repair gasdermin and perforin pores. | Nature | 107 | 35705808 |
| 2008 | Corticosteroids reduce IL-6 in ASM cells via up-regulation of MKP-1. | American journal of respiratory cell and molecular biology | 104 | 18314542 |
| 2011 | Modeling nitrous oxide production during biological nitrogen removal via nitrification and denitrification: extensions to the general ASM models. | Environmental science & technology | 102 | 21780759 |
| 1996 | Asm-1+, a Neurospora crassa gene related to transcriptional regulators of fungal development. | Genetics | 95 | 8913744 |
| 2001 | Pimecrolimus (Elidel, SDZ ASM 981)--preclinical pharmacologic profile and skin selectivity. | Seminars in cutaneous medicine and surgery | 92 | 11770910 |
| 2019 | SMPD1 mutations, activity, and α-synuclein accumulation in Parkinson's disease. | Movement disorders : official journal of the Movement Disorder Society | 90 | 30788890 |
| 1998 | The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion. | The British journal of dermatology | 90 | 9990361 |
| 2002 | Low systemic exposure after repeated topical application of Pimecrolimus (Elidel), SD Z ASM 981) in patients with atopic dermatitis. | Dermatology (Basel, Switzerland) | 89 | 11834853 |
| 2006 | IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM. | American journal of physiology. Lung cellular and molecular physiology | 88 | 16684953 |
| 2001 | The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) is a potent inhibitor of mediator release from human dermal mast cells and peripheral blood basophils. | The Journal of allergy and clinical immunology | 84 | 11496246 |
| 2013 | Rare lysosomal enzyme gene SMPD1 variant (p.R591C) associates with Parkinson's disease. | Neurobiology of aging | 80 | 23871123 |
| 2012 | Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients. | Molecular genetics and metabolism | 77 | 22818240 |
| 2015 | SMPD1 Mutation Update: Database and Comprehensive Analysis of Published and Novel Variants. | Human mutation | 65 | 26499107 |
| 1998 | Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner. | Archives of dermatological research | 60 | 9808344 |
| 1991 | Regional assignment of the human acid sphingomyelinase gene (SMPD1) by PCR analysis of somatic cell hybrids and in situ hybridization to 11p15.1----p15.4. | Genomics | 58 | 2004772 |
| 2018 | Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM. | Neuron | 52 | 30269989 |
| 2015 | The contribution of Niemann-Pick SMPD1 mutations to Parkinson disease in Ashkenazi Jews. | Parkinsonism & related disorders | 51 | 26169695 |
| 1991 | The human ASM (adult skeletal muscle) gene: expression and chromosomal assignment to 11p15. | Biochemical and biophysical research communications | 48 | 1953776 |
| 2006 | Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient Niemann-Pick disease. | American journal of human genetics | 43 | 16642440 |
| 2006 | Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration. | Nature protocols | 43 | 17406553 |
| 2003 | Compound heterozygosity at the sphingomyelin phosphodiesterase-1 (SMPD1) gene is associated with low HDL cholesterol. | Human genetics | 41 | 12607113 |
| 2012 | TRAIL death receptor 4 signaling via lysosome fusion and membrane raft clustering in coronary arterial endothelial cells: evidence from ASM knockout mice. | Journal of molecular medicine (Berlin, Germany) | 40 | 23108456 |
| 2009 | Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients. | Human mutation | 40 | 19405096 |
| 2008 | Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models. | Molecular genetics and metabolism | 40 | 18815062 |
| 2016 | Acid Sphingomyelinase (ASM) is a Negative Regulator of Regulatory T Cell (Treg) Development. | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 39 | 27512981 |
| 2020 | Comparative lipidomics of 5-Fluorouracil-sensitive and -resistant colorectal cancer cells reveals altered sphingomyelin and ceramide controlled by acid sphingomyelinase (SMPD1). | Scientific reports | 38 | 32273521 |
| 2019 | Medial calcification in the arterial wall of smooth muscle cell-specific Smpd1 transgenic mice: A ceramide-mediated vasculopathy. | Journal of cellular and molecular medicine | 36 | 31743567 |
| 2015 | The emerging role of SMPD1 mutations in Parkinson's disease: Implications for future studies. | Parkinsonism & related disorders | 35 | 26320887 |
| 2014 | Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca(2+) regulation in airway smooth muscle (ASM). | Canadian journal of physiology and pharmacology | 35 | 25506723 |
| 2010 | Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease. | Molecular medicine (Cambridge, Mass.) | 34 | 20386867 |
| 2020 | Impact of metal-oxide nanoparticles on growth, physiology and yield of tomato (Solanum lycopersicum L.) modulated by Azotobacter salinestris strain ASM. | Environmental pollution (Barking, Essex : 1987) | 32 | 33316490 |
| 2003 | Establishment and characterization of an angiosarcoma-derived cell line, AS-M. | Endothelium : journal of endothelial cell research | 32 | 14741847 |
| 2018 | Contribution of p62/SQSTM1 to PDGF-BB-induced myofibroblast-like phenotypic transition in vascular smooth muscle cells lacking Smpd1 gene. | Cell death & disease | 31 | 30451833 |
| 2012 | ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target. | PloS one | 31 | 23049887 |
| 2021 | Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation. | Lipids in health and disease | 30 | 33612104 |
| 2005 | Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick Type B disease. | Human mutation | 29 | 16010684 |
| 2016 | SMPD1 variants in Chinese Han patients with sporadic Parkinson's disease. | Parkinsonism & related disorders | 27 | 27814975 |
| 2013 | Identification of a distinct mutation spectrum in the SMPD1 gene of Chinese patients with acid sphingomyelinase-deficient Niemann-Pick disease. | Orphanet journal of rare diseases | 27 | 23356216 |
| 2021 | Ceramide-Induced Lysosomal Biogenesis and Exocytosis in Early-Onset Preeclampsia Promotes Exosomal Release of SMPD1 Causing Endothelial Dysfunction. | Frontiers in cell and developmental biology | 25 | 34017832 |
| 2018 | Sphingomyelin phosphodiesterase 1 (SMPD1) mediates the attenuation of myocardial infarction-induced cardiac fibrosis by astaxanthin. | Biochemical and biophysical research communications | 25 | 29906461 |
| 2013 | Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B. | Clinical genetics | 24 | 23252888 |
| 2015 | Epidemiological, clinical and biochemical characterization of the p.(Ala359Asp) SMPD1 variant causing Niemann-Pick disease type B. | European journal of human genetics : EJHG | 22 | 25920558 |
| 2004 | Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1. | Human mutation | 22 | 15221801 |
| 2012 | Integrin and GPCR Crosstalk in the Regulation of ASM Contraction Signaling in Asthma. | Journal of allergy | 21 | 23056062 |
| 2020 | Homozygous Smpd1 deficiency aggravates brain ischemia/ reperfusion injury by mechanisms involving polymorphonuclear neutrophils, whereas heterozygous Smpd1 deficiency protects against mild focal cerebral ischemia. | Basic research in cardiology | 20 | 33057972 |
| 2016 | Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells. | Biochemical and biophysical research communications | 19 | 26809095 |
| 2015 | Systematic Genetic Analysis of the SMPD1 Gene in Chinese Patients with Parkinson's Disease. | Molecular neurobiology | 19 | 26377108 |
| 2016 | Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells. | Journal of cellular physiology | 18 | 26825339 |
| 2006 | Assays for in vitro monitoring of proliferation of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cells. | Nature protocols | 18 | 17406550 |
| 2016 | Regulation of dynein-mediated autophagosomes trafficking by ASM in CASMCs. | Frontiers in bioscience (Landmark edition) | 16 | 26709800 |
| 2014 | Anti-CTGF single-chain variable fragment dimers inhibit human airway smooth muscle (ASM) cell proliferation by down-regulating p-Akt and p-mTOR levels. | PloS one | 16 | 25478966 |
| 2021 | mRNA Expression of SMPD1 Encoding Acid Sphingomyelinase Decreases upon Antidepressant Treatment. | International journal of molecular sciences | 13 | 34071826 |
| 2021 | ORMDL3 expression in ASM regulates hypertrophy, hyperplasia via TPM1 and TPM4, and contractility. | JCI insight | 12 | 33661765 |
| 2021 | Sortilin deletion in the prefrontal cortex and hippocampus ameliorates depressive-like behaviors in mice via regulating ASM/ceramide signaling. | Acta pharmacologica Sinica | 12 | 34931016 |
| 2016 | Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease. | American journal of medical genetics. Part A | 12 | 27338287 |
| 2015 | Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand. | International archives of allergy and immunology | 12 | 25660404 |
| 2021 | Aspulvinones Suppress Postprandial Hyperglycemia as Potent α-Glucosidase Inhibitors From Aspergillus terreus ASM-1. | Frontiers in chemistry | 11 | 34485249 |
| 2018 | Inhibition of ASM activity ameliorates DSS-induced colitis in mice. | Prostaglandins & other lipid mediators | 11 | 30550872 |
| 2015 | Alternative splicing of SMPD1 in human sepsis. | PloS one | 11 | 25898364 |
| 2014 | Bronchodilatory and anti-inflammatory effects of ASM-024, a nicotinic receptor ligand, developed for the treatment of asthma. | PloS one | 11 | 24465890 |
| 2023 | KCNQ2-Related Epilepsy: Genotype-Phenotype Relationship with Tailored Antiseizure Medication (ASM)-A Systematic Review. | Neuropediatrics | 10 | 36948217 |
| 2022 | Optimization of 3D-aggregated spheroid model (3D-ASM) for selecting high efficacy drugs. | Scientific reports | 10 | 36344810 |
| 2015 | Four novel p.N385K, p.V36A, c.1033-1034insT and c.1417-1418delCT mutations in the sphingomyelin Phosphodiesterase 1 (SMPD1) gene in patients with types A and B Niemann-Pick disease (NPD). | International journal of molecular sciences | 10 | 25811928 |
| 2002 | Platelet aggregation and intracellular calcium mobilisation responses are enhanced by cyclosporin A but not by pimecrolimus (SDZ ASM 981). | Platelets | 10 | 12189022 |
| 2024 | ASM variants in the spotlight: A structure-based atlas for unraveling pathogenic mechanisms in lysosomal acid sphingomyelinase. | Biochimica et biophysica acta. Molecular basis of disease | 9 | 38782304 |
| 2020 | Fibrocyte localisation to the ASM bundle in asthma: bidirectional effects on cell phenotype and behaviour. | Clinical & translational immunology | 9 | 33209301 |
| 2019 | Niemann-Pick disease A or B in four pediatric patients and SMPD1 mutation carrier frequency in the Mexican population. | Annals of hepatology | 9 | 31122880 |
| 2016 | LRRK2, GBA and SMPD1 Founder Mutations and Parkinson's Disease in Ashkenazi Jews. | Dementia and geriatric cognitive disorders | 9 | 27449028 |
| 1993 | Effects of substrate and inhibition of oxidative metabolism on contraction and myosin phosphorylation in ASM. | The American journal of physiology | 9 | 8333548 |
| 2023 | Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study. | Neurology and therapy | 8 | 37707705 |
| 2021 | Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency. | Human mutation | 8 | 34273913 |
| 2020 | An Early-Onset Neuronopathic Form of Acid Sphingomyelinase Deficiency: A SMPD1 p.C133Y Mutation in the Saposin Domain of Acid Sphingomyelinase. | The Tohoku journal of experimental medicine | 8 | 31941852 |
| 2014 | Neurospora crassa ASM-1 complements the conidiation defect in a stuA mutant of Aspergillus nidulans. | Mycologia | 8 | 25550299 |
| 2007 | Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol. | BMC medical genetics | 8 | 18088425 |
| 2023 | The lipidomes of C. elegans with mutations in asm-3/acid sphingomyelinase and hyl-2/ceramide synthase show distinct lipid profiles during aging. | Aging | 7 | 36787434 |
| 2015 | Alleged Detrimental Mutations in the SMPD1 Gene in Patients with Niemann-Pick Disease. | International journal of molecular sciences | 7 | 26084044 |
| 2015 | Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma. | Canadian respiratory journal | 7 | 26252534 |
| 2013 | New Single Nucleotide Deletion In the SMPD1 Gene Causes Niemann Pick Disease Type A in a Child from Southwest Iran: A Case Report. | Iranian journal of pediatrics | 7 | 23724191 |
| 2005 | 2004 ASM Conference on the New Phage Biology: the 'Phage Summit'. | Molecular microbiology | 7 | 15720541 |
| 2024 | Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry. | Journal of movement disorders | 6 | 38291878 |
| 2022 | Autophagic secretion of mitochondria (ASM): an alternative way for getting rid of damaged mitochondria. | Autophagy | 6 | 35900940 |
| 2020 | Mutational spectrum of SMPD1 gene in Pakistani Niemann-Pick disease patients. | Pakistan journal of medical sciences | 6 | 32292456 |
| 2019 | An induced pluripotent stem cell line (TRNDi009-C) from a Niemann-Pick disease type A patient carrying a heterozygous p.L302P (c.905 T>C) mutation in the SMPD1 gene. | Stem cell research | 6 | 31132580 |
| 2016 | Decreasing SMPD1 activity in BEAS-2B bronchial airway epithelial cells results in increased NRF2 activity, cytokine synthesis and neutrophil recruitment. | Biochemical and biophysical research communications | 6 | 27865842 |
| 2014 | A novel missense SMPD1 gene mutation, T460P, and clinical findings in a patient with Niemann-Pick disease type B presenting to a lipid disorders clinic. | Annals of clinical biochemistry | 6 | 24643943 |
| 2012 | R542X mutation in SMPD1 gene: genetically novel mutation with phenotypic features intermediate between type A and type B Niemann-Pick disease. | BMJ case reports | 6 | 23188845 |
| 2011 | Reduced cellular cholesterol efflux and low plasma high-density lipoprotein cholesterol in a patient with type B Niemann-Pick disease because of a novel SMPD-1 mutation. | Journal of clinical lipidology | 6 | 22264577 |
| 2023 | Discovery of Novel N-Hydroxy-1,2,4-oxadiazole-5-formamides as ASM Direct Inhibitors for the Treatment of Atherosclerosis. | Journal of medicinal chemistry | 5 | 36786607 |
| 2022 | Expanding ASM models towards integrated processes for short-cut nitrogen removal and bioplastic recovery. | The Science of the total environment | 5 | 35104516 |
| 2017 | Doxofylline does not increase formoterol-induced cAMP nor MKP-1 expression in ASM cells resulting in lack of anti-inflammatory effect. | Pulmonary pharmacology & therapeutics | 5 | 28414142 |
| 2016 | Seven novel mutations of the SMPD1 gene in four Chinese patients with Niemann-Pick disease type A and prenatal diagnosis for four fetuses. | European journal of medical genetics | 5 | 26851525 |
| 2013 | Analysis of the sphingomyelin phosphodiesterase 1 gene (SMPD1) in Turkish Niemann-Pick disease patients: mutation profile and description of a novel mutation. | Gene | 5 | 23618813 |
| 2023 | Acid sphingomyelinase (ASM) and COVID-19: A review of the potential use of ASM inhibitors against SARS-CoV-2. | Cell biochemistry and function | 4 | 36929117 |
| 2022 | Compound Heterozygote Mutation in the SMPD1 Gene Leading to Nieman-Pick Disease Type A. | The American journal of case reports | 4 | 36333862 |