Factors that promote inflammation in C9ORF72 mutation carriers with amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) have remained elusive. McCourt et al. identified pro-inflammatory forms of glycogen in gut contents of people with ALS/FTD and demonstrate that targeting glycogen in a C9orf72 mouse model extends lifespan and reduces neuroinflammation.