Taken together, the RNAi-mediated knockdown of either the Gba1a or Gba1b Drosophila orthologs of the human GBA1 gene proved able to strikingly recapitulate key pathogenic features of Gaucher disease, strongly supporting the in vivo power and value of the fly brain–midgut axis for reliably modeling and illuminating disease mechanisms and promptly discovering therapeutic regimens. The gene discussed is GBA1; the disease is Gaucher disease.