VAC14 and amyotrophic lateral sclerosis: While no human mutations in PIK3C3, the gene encoding Vps34, have been associated with neurodegenerative disorders, the relevance of the PI3P/PI(3,5)P2 pathway in neurological disorders is supported by the existence of amyotrophic lateral sclerosis (ALS) and Charcot–Marie–Tooth 4 J (CMT4J) causing mutations in FIG4 as well as PD causing mutations in VAC14, both of which are key components of the PIKfyve complex controlling PI(3,5)P2 metabolism11,14.