Massive cellular accumulation of GluCer/GlcSph due to Gba deficiency in microglia, immune infiltrates, and neurons resulted in early onset of neuroinflammation, which was attenuated into late-onset neurodegenerative disease by selective rescue of Gba in either microglia or neurons as well as by pharmacological reduction of GluCer/GlcSph in the brain using GCS inhibitor. Here, GBA1 is linked to neurodegenerative disease.