Ubiquilin 2: a component of the ubiquitin-proteasome system with an emerging role in neurodegeneration

Int J Biochem Cell Biol. 2014 May:50:123-6. doi: 10.1016/j.biocel.2014.02.018. Epub 2014 Feb 28.


Ubiquilin 2, which is encoded by the UBQLN2 gene, plays a critical role in protein clearance pathways including the ubiquitin-proteasome system and autophagy. Ubiquilin 2 physically associates with ubiquitin ligases and proteasomes to mediate protein degradation. It also plays a role in the regulation of cell signalling and cell cycle progression, and association with cytoskeletal elements. Recent studies have revealed that ubiquilin 2 also plays a pathogenic role in neurodegenerative disease, including amyotrophic lateral sclerosis (ALS), and ALS-frontotemporal dementia (ALS-FTD). Rare UBQLN2 mutations cause a small subset of ALS and ALS-FTD cases. More widespread is the presence of ubiquilin 2 positive inclusions in the affected neurons of some familial and sporadic ALS and ALS-FTD patients. These discoveries have led to the hypothesis that perturbation in protein clearance, mediated by ubiquilin 2, is an important pathogenic mechanism in neurodegeneration.

Keywords: Amyotrophic lateral sclerosis; Autophagy; Dementia; Ubiquilin 2; Ubiquitin–proteasome system.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • Autophagy-Related Proteins
  • Cell Cycle Proteins / metabolism
  • Dementia / etiology*
  • Humans
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Ubiquitins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • Cell Cycle Proteins
  • UBQLN2 protein, human
  • Ubiquitins
  • Proteasome Endopeptidase Complex

Supplementary concepts

  • Amyotrophic lateral sclerosis 1