GSK3β has been shown to be activated upon expression of ALS/FTD-linked genes TDP-43 and FUS, leading to decreased ER–mitochondria connectivity and a concomitant decrease in the levels of mitochondrial Ca2+ (Stoica et al, 2014, 2016), potentially altering the mitochondrial bioenergetics. This evidence concerns the gene GSK3B and amyotrophic lateral sclerosis.