Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis

Biochim Biophys Acta. 2014 Mar;1841(3):353-61. doi: 10.1016/j.bbalip.2013.11.009. Epub 2013 Nov 27.


X-linked ichthyosis is a relatively common syndromic form of ichthyosis most often due to deletions in the gene encoding the microsomal enzyme, steroid sulfatase, located on the short area of the X chromosome. Syndromic features are mild or unapparent unless contiguous genes are affected. In normal epidermis, cholesterol sulfate is generated by cholesterol sulfotransferase (SULT2B1b), but desulfated in the outer epidermis, together forming a 'cholesterol sulfate cycle' that potently regulates epidermal differentiation, barrier function and desquamation. In XLI, cholesterol sulfate levels my exceed 10% of total lipid mass (≈1% of total weight). Multiple cellular and biochemical processes contribute to the pathogenesis of the barrier abnormality and scaling phenotype in XLI. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

Keywords: Cholesterol sulfate; Corneodesmosomes; Epidermal barrier function; Epidermal lipid metabolism; Steroid sulfatase; X-linked ichthyosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Differentiation / genetics*
  • Cholesterol Esters* / genetics
  • Cholesterol Esters* / metabolism
  • Epidermis* / enzymology
  • Epidermis* / ultrastructure
  • Female
  • Humans
  • Ichthyosis, X-Linked* / enzymology
  • Ichthyosis, X-Linked* / genetics
  • Ichthyosis, X-Linked* / pathology
  • Male
  • Sulfotransferases* / genetics
  • Sulfotransferases* / metabolism


  • Cholesterol Esters
  • Sulfotransferases
  • SULT2B1 protein, human
  • cholesteryl sulfate