Approved enzyme replacement therapies for Gaucher's disease do not help neurological symptoms. Vitner et al. used a mouse model of Gaucher's disease to show that neuronal cell death hinged on a pathway of programmed cell necrosis that involved the kinases RIPK1 (receptor-interacting protein kinase 1) and RIPK3. Mice that were deficient in RIPK3 had less neuronal loss and liver injury, improved motor coordination and a longer lifespan than mouse models with normal RIPK3 expression, suggesting that RIPK3 could be a new target for the disorder.