Fatty Acid 2-Hydroxylase and 2-Hydroxylated Sphingolipids: Metabolism and Function in Health and Diseases

Int J Mol Sci. 2023 Mar 3;24(5):4908. doi: 10.3390/ijms24054908.


Sphingolipids containing acyl residues that are hydroxylated at C-2 are found in most, if not all, eukaryotes and certain bacteria. 2-hydroxylated sphingolipids are present in many organs and cell types, though they are especially abundant in myelin and skin. The enzyme fatty acid 2-hydroxylase (FA2H) is involved in the synthesis of many but not all 2-hydroxylated sphingolipids. Deficiency in FA2H causes a neurodegenerative disease known as hereditary spastic paraplegia 35 (HSP35/SPG35) or fatty acid hydroxylase-associated neurodegeneration (FAHN). FA2H likely also plays a role in other diseases. A low expression level of FA2H correlates with a poor prognosis in many cancers. This review presents an updated overview of the metabolism and function of 2-hydroxylated sphingolipids and the FA2H enzyme under physiological conditions and in diseases.

Keywords: cancer; fatty acid 2-hydroxylase; fatty acid hydroxylase-associated neurodegeneration; hereditary spastic paraplegia; leukodystrophy; myelin; neurodegeneration; neurodegeneration with brain iron accumulation; skin; sphingolipids.

Publication types

  • Review

MeSH terms

  • Fatty Acids / metabolism
  • Humans
  • Mixed Function Oxygenases* / metabolism
  • Myelin Sheath / metabolism
  • Neurodegenerative Diseases* / metabolism
  • Sphingolipids* / metabolism


  • Fatty Acids
  • Mixed Function Oxygenases
  • Sphingolipids
  • fatty acid alpha-hydroxylase

Grants and funding

This research received no external funding.