Acid ceramidase and the treatment of ceramide diseases: The expanding role of enzyme replacement therapy

Biochim Biophys Acta. 2016 Sep;1862(9):1459-71. doi: 10.1016/j.bbadis.2016.05.001. Epub 2016 May 4.


Ceramides are a diverse group of sphingolipids that play important roles in many biological processes. Acid ceramidase (AC) is one key enzyme that regulates ceramide metabolism. Early research on AC focused on the fact that it is the enzyme deficient in the rare genetic disorder, Farber Lipogranulomatosis. Recent research has revealed that deficiency of the same enzyme is responsible for a rare form of spinal muscular atrophy associated with myoclonic epilepsy (SMA-PME). Due to their diverse role in biology, accumulation of ceramides also has been implicated in the pathobiology of many other common diseases, including infectious lung diseases, diabetes, cancers and others. This has revealed the potential of AC as a therapy for many of these diseases. This review will focus on the biology of AC and the potential role of this enzyme in the treatment of human disease.

Keywords: Cell signaling; Ceramide; Enzymes; Lysosomal storage diseases; Sphingolipids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acid Ceramidase / genetics
  • Acid Ceramidase / therapeutic use*
  • Animals
  • Arthritis / drug therapy
  • Arthritis / metabolism
  • Bacterial Infections / drug therapy
  • Bacterial Infections / metabolism
  • Ceramides / metabolism*
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / metabolism
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism
  • Disease Models, Animal
  • Enzyme Replacement Therapy*
  • Epilepsies, Myoclonic / complications
  • Epilepsies, Myoclonic / drug therapy
  • Epilepsies, Myoclonic / metabolism
  • Farber Lipogranulomatosis / drug therapy*
  • Farber Lipogranulomatosis / genetics
  • Farber Lipogranulomatosis / metabolism*
  • Humans
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / metabolism
  • Mice
  • Mice, Knockout
  • Muscular Atrophy, Spinal / complications
  • Muscular Atrophy, Spinal / drug therapy
  • Muscular Atrophy, Spinal / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Retinal Degeneration / drug therapy
  • Retinal Degeneration / metabolism
  • Sphingolipidoses / drug therapy
  • Sphingolipidoses / genetics
  • Sphingolipidoses / metabolism


  • Ceramides
  • ASAH1 protein, human
  • Acid Ceramidase
  • Asah1 protein, mouse