Invisible leashes: The tethering VAPs from infectious diseases to neurodegeneration

J Biol Chem. 2021 Jan-Jun:296:100421. doi: 10.1016/j.jbc.2021.100421. Epub 2021 Feb 18.


Intracellular organelles do not, as thought for a long time, act in isolation but are dynamically tethered together by entire machines responsible for interorganelle trafficking and positioning. Among the proteins responsible for tethering is the family of VAMP-associated proteins (VAPs) that appear in all eukaryotes and are localized primarily in the endoplasmic reticulum. The major functional role of VAPs is to tether the endoplasmic reticulum with different organelles and regulate lipid metabolism and transport. VAPs have gained increasing attention because of their role in human pathology where they contribute to infections by viruses and bacteria and participate in neurodegeneration. In this review, we discuss the structure, evolution, and functions of VAPs, focusing more specifically on VAP-B for its relationship with amyotrophic lateral sclerosis and other neurodegenerative diseases.

Keywords: ALS; VAMP; endoplasmic reticulum; tethering proteins.

Publication types

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

MeSH terms

  • Animals
  • Communicable Diseases / metabolism*
  • Humans
  • Lipid Metabolism
  • Mutation
  • Neurodegenerative Diseases / metabolism*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • VAPB protein, human
  • Vesicular Transport Proteins