The endoplasmic reticulum (ER) and mitochondria connect at multiple contact 
sites to form a unique cellular compartment, termed the 'mitochondria-associated 
ER membranes' (MAMs). MAMs are hubs for signalling pathways that regulate 
cellular homeostasis and survival, metabolism, and sensitivity to apoptosis. 
MAMs are therefore involved in vital cellular functions, but they are 
dysregulated in several human diseases. Whilst MAM dysfunction is increasingly 
implicated in the pathogenesis of neurodegenerative diseases, its role in 
amyotrophic lateral sclerosis (ALS) is poorly understood. However, in ALS both 
ER and mitochondrial dysfunction are well documented pathophysiological events. 
Moreover, alterations to lipid metabolism in neurons regulate processes linked 
to neurodegenerative diseases, and a link between dysfunction of lipid 
metabolism and ALS has also been proposed. In this review we discuss the 
structural and functional relevance of MAMs in ALS and how targeting MAM could 
be therapeutically beneficial in this disorder.