In this regard, in apparent self-contradiction and in contrast with the view that dysproteostasis caused by malfunction of degradation machinery contributes to motor neuron failure in ALS, studies from our laboratory on a mutant form of the VAPB gene product, associated with a rare form of FALS, indicate that mutant VAPB generates unusual inclusions, which are easily cleared by cells and do not affect either UPS or autophagy. Here, VAPB is linked to amyotrophic lateral sclerosis.