VAP-B and its role in Amyotrophic lateral sclerosis The document discusses VAP-B and its role in Amyotrophic lateral sclerosis (ALS). ALS is a neurodegenerative disorder characterized by motor neuron death. The P56S mutation in VAP-B has been linked to familial ALS and causes protein aggregation, ubiquitination, and insolubility. The mutation induces conformational changes in VAP-B that enhance oligomerization and prevent interaction with lipid transfer proteins, impairing membrane trafficking and lipid homeostasis. This leads to endoplasmic reticulum stress, proteasomal dysfunction, and motor neuron degeneration.