Thus, four different FTD/ALS-linked genetic insults, TDP-43, FUS, the Sigma-1 receptor and mutant SOD1, have all been shown to disrupt ER−mitochondria contacts and signalling and where investigated (TDP-43 and FUS) this involves breaking of the VAPB−PTPIP51 tethers80,89,93,94,98. This evidence concerns the gene FUS and amyotrophic lateral sclerosis.