beta-glucosylceramide (beta-GlcCer) accumulates in Gaucher disease, but how beta-GlcCer, a Mincle ligand, causes characteristic neuroinflammation and neuronopathy is poorly understood. In this issue of Immunity, Shimizu et al. reveal that Mincle-dependent activation of microglia led to phagocytosis of neurons and neurologic symptoms.