To determine if the IP3R–GRP75–VDAC1 signaling axis, which has been implicated in the progression of other neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Amyotrophic Lateral Sclerosis, undergoes reorganization in NPC disease we took a two-pronged approach leveraging NPC1−/− cells and neurons treated with U18. This evidence concerns the gene NPC1 and amyotrophic lateral sclerosis.