Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by 
progressive neuromuscular junction (NMJ) dismantling and degeneration of motor 
neurons leading to atrophy and paralysis of voluntary muscles responsible for 
motion and breathing. Except for a minority of patients harbouring genetic 
mutations, the origin of most ALS cases remains elusive. Peripheral tissues, and 
particularly skeletal muscle, have lately demonstrated an active contribution to 
disease pathology attracting a growing interest for these tissues as therapeutic 
targets in ALS. In this sense, molecular mechanisms essential for cell and 
tissue homeostasis have been shown to be deregulated in the disease. These 
include muscle metabolism and mitochondrial activity, RNA processing, 
tissue-resident stem cell function responsible for muscle regeneration, and 
proteostasis that regulates muscle mass in adulthood. This review aims to 
compile scientific evidence that demonstrates the role of skeletal muscle in ALS 
pathology and serves as reference for development of novel therapeutic 
strategies targeting this tissue to delay disease onset and progression. LINKED 
ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To 
view the other articles in this section visit 
http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc.