Sitosterolemia: Twenty years of discovery of the function of abcg5 abcg8

Kori Williams, Allison Segard, Gregory A. Graf

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations


Sitosterolemia is a lipid disorder characterized by the accumulation of dietary xenosterols in plasma and tissues caused by mutations in either ABCG5 or ABCG8. ABCG5 ABCG8 encodes a pair of ABC half transporters that form a heterodimer (G5G8), which then traffics to the surface of hepatocytes and enterocytes and promotes the secretion of cholesterol and xenosterols into the bile and the intestinal lumen. We review the literature from the initial description of the disease, the discovery of its genetic basis, current therapy, and what has been learned from animal, cellular, and molecular investigations of the transporter in the twenty years since its discovery. The genomic era has revealed that there are far more carriers of loss of function mutations and likely pathogenic variants of ABCG5 ABCG8 than previously thought. The impact of these variants on G5G8 structure and activity are largely unknown. We propose a classification system for ABCG5 ABCG8 mutants based on previously published systems for diseases caused by defects in ABC transporters. This system establishes a framework for the comprehensive analysis of disease‐associated variants and their impact on G5G8 structure–function.

Original languageEnglish
Article number2641
Pages (from-to)1-14
Number of pages14
JournalInternational Journal of Molecular Sciences
Issue number5
StatePublished - Mar 1 2021

Bibliographical note

Funding Information:
This research was funded by the National Institutes of Health, grant numbers 1R01DK113625, 1P20GM130456, 5P30GM127211.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • ABC
  • Atherosclerosis
  • Cholesterol
  • Gall stone
  • Phytosterol
  • Transporter
  • Xenosterol

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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