Such findings are in line with a recent elegant study that identified lowered ATP production by mitochondria as driver of motor neuron degeneration in ALS [70]; the TDP-43 and Sigma 1 receptor loss-induced loosening of ER–mitochondria associations are predicted to lower mitochondrial ATP production 18, 19, 20, 21. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.