To explore the mechanism by which mutations in GBA1 lead to neurodegenerative diseases, we created a Drosophila model of glucocerebrosidase deficiency by generating a deletion of the Drosophila GBA1 homolog dGBA1b. Drosophila dGBA1b mutants exhibit shortened lifespan, locomotor, memory and other behavioral deficits, neurodegeneration, and accumulation of insoluble protein aggregates that are normally degraded through an autophagic process. This evidence concerns the gene GBA1 and neurodegenerative disease.