In summary, our findings show that ALS/FTD‐associated C9orf72 damages ER‐mitochondria contacts, IP3 receptor‐mediated delivery of Ca2+ to mitochondria and that this damage may involve DPR‐mediated activation of GSK3β and disruption of the VAPB‐PTPIP51 tethering proteins. This evidence concerns the gene RMDN3 and frontotemporal dementia.