The role of FUS gene variants in neurodegenerative diseases

Nat Rev Neurol. 2014 Jun;10(6):337-48. doi: 10.1038/nrneurol.2014.78. Epub 2014 May 20.


The neurodegenerative diseases are a diverse group of disorders characterized by progressive loss of specific groups of neurons. These diseases affect different populations, and have a variable age of onset, clinical symptoms, and pathological findings. Variants in the FUS gene, which encodes an RNA-binding protein, have been identified as causative or risk factors for amyotrophic lateral sclerosis (ALS), essential tremor and rare forms of frontotemporal lobar degeneration (FTLD). Additionally, abnormal aggregation of FUS protein has been reported in multiple neurodegenerative diseases, including ALS, FTLD and the polyglutamine diseases, suggesting a role for FUS in the pathogenesis of these neurodegenerative diseases. This Review summarizes current understanding of the normal function of FUS, and describes its role in the pathology of ALS, FTLD, essential tremor and other neurodegenerative diseases. Comments on the underlying pathogenetic mechanisms of these FUS-related disorders are included. Finally, the clinical implications of recent advances in FUS research are discussed. Further understanding of the role of FUS in neurodegenerative diseases might lead to improvements in the treatment and prevention of these disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Neurodegenerative Diseases / genetics*
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / physiology*


  • RNA-Binding Protein FUS