{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:38:36Z","timestamp":1791290316871,"version":"4.3.0"},"reference-count":94,"publisher":"Walter de Gruyter GmbH","issue":"6-7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p>Acid ceramidase (N-acylsphingosine deacylase, EC 3.5.1.23; AC) is the lipid hydrolase responsible for the degradation of ceramide into sphingosine and free fatty acids within lysosomes. The enzymatic activity was first identified over four decades ago and is deficient in two rare inherited disorders, Farber lipogranulomatosis (Farber disease) and spinal muscular atrophy with myoclonic epilepsy (SMA-PME). Importantly, AC not only hydrolyzes ceramide into sphingosine within acidic compartments, but also can synthesize ceramide from sphingosine at neutral pH, suggesting that the enzyme may have diverse functions depending on its subcellular location and the local pH. Within cells, AC exists in a complex with other lipid hydrolases and requires a polypeptide cofactor (saposin D) for full hydrolytic activity. Recent studies also have shown that AC is overexpressed in several human cancers, and that inhibition of this enzyme may be a useful cancer drug target. Aberrant AC activity has also been described in several other common diseases. The cDNA and gene (<jats:italic>ASAH1<\/jats:italic>) encoding AC have been isolated, several mouse models of AC deficiency have been constructed, and the recombinant enzyme is currently being manufactured for the treatment of Farber disease and SMA-PME. Current information concerning the biology of this enzyme and its role in human disease is reviewed within.<\/jats:p>","DOI":"10.1515\/hsz-2014-0290","type":"journal-article","created":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T17:01:09Z","timestamp":1430758869000},"page":"759-765","source":"Crossref","is-referenced-by-count":29,"title":["The molecular medicine of acid ceramidase"],"prefix":"10.1515","volume":"396","author":[{"given":"Michael","family":"Frohbergh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Schuchman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref81","first-page":"464","article-title":"Effective inhibition of acid and neutral ceramidases by novel lcl 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ceramides","author":"Enzymic","year":"1963","journal-title":"Biol Chem"},{"key":"ref281","first-page":"276","article-title":"Interfacial regulation of acid ceramidase activity Stimulation of ceramide degradation by lysosomal lipids and sphingolipid activator proteins","author":"Linke","year":"2001","journal-title":"Biol Chem"},{"key":"ref291","first-page":"2015","article-title":"Madeira Advanced cell therapies for articular cartilage regeneration","author":"Santhagunam","journal-title":"Trends Biotechnol"},{"key":"ref371","first-page":"1233","article-title":"Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer","author":"Selzner","year":"2001","journal-title":"Cancer Res"},{"key":"ref881","first-page":"178","article-title":"deficiency in disease lipogranulomatosis","author":"Sugita","year":"1972","journal-title":"Science"},{"key":"ref61","first-page":"331","article-title":"Edelmann Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons Front","author":"Beckmann","year":"2014"},{"key":"ref411","first-page":"178","article-title":"deficiency in disease lipogranulomatosis","author":"Sugita","year":"1972","journal-title":"Science"},{"key":"ref921","first-page":"305","article-title":"s disease type iv presenting with cholestasis and neonatal liver failure : report of two cases","volume":"11","author":"Willis","year":"2008"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1096\/fj.09-145508","article-title":"Acid ceramidase improves the quality of oocytes and embryos and the outcome ofin vitrofertilization","volume":"24","author":"Eliyahu","year":"2010","journal-title":"FASEB J"},{"key":"ref691","first-page":"278","article-title":"Purification and characterization of recombinant human acid ceramidase Catalytic reactions and interactions with acid sphingomyelinase","author":"He","year":"2003","journal-title":"Biol Chem"},{"key":"ref321","first-page":"278","article-title":"The reverse activity of human acid ceramidase","author":"Okino","year":"2003","journal-title":"Biol Chem"},{"key":"ref381","first-page":"283","article-title":"cleavage and activation of human acid ceramidase","author":"Shtraizent","year":"2008","journal-title":"Biol Chem"},{"key":"ref561","first-page":"508","article-title":"cftr corrector lumacaftor and a cftr potentiator ivacaftor for treatment of patients with cystic fibrosis who have a del mutation a phase randomised controlled trial","author":"Boyle","year":"2014","journal-title":"Lancet Med"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/cge.12307","article-title":"Evidence for clinical genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy","author":"Dyment","year":"2014","journal-title":"Clin Genet"},{"key":"ref191","first-page":"238","article-title":"Gatt hydrolysis and synthesis of 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