•Abnormal accumulation of proteins and stress granules was observed in c9orf72 IPSC-derived MNs.•Decreased survival of these cells may be due to disruption of mitochondrial membrane potential and calcium homeostasis, increased ER stress and decreased BCL2 protein levels.•By examining the effects of C9orf72 mutations on calcium signaling pathways, the importance of this pathway as a therapeutic target in neurodegenerative disease was determined. Here, BCL2 is linked to neurodegenerative disease.