Hereditary spastic paraplegias (HSPs) are genetic diseases characterised by spasticity and weakness of the lower limbs that result from axonal defects. Mutations in a few ER-membrane-shaping proteins, including Atlastin, give rise to more than 60% of HSPs. Atlastin is a conserved, dynamin-related GTPase that controls ER structure by mediating the fusion of ER tubules. Atlastin mutations that cause HSP suggest that aberrant ER morphology is a key factor contributing to pathology. In this work (p. 3507), Andrés Couve and co-workers address the molecular role of neuronal Atlastin in a Drosophila model by analysing its effects on locomotor behaviour, synaptic function, secretory organelle distribution and ultrastructure of the synapse. They show that altered levels of Atlastin gives rise to severe locomotion defects in larvae and adults, and that loss of Atlastin in motor neurons impairs synaptic function affecting a specific release component. These effects correlate with observed abnormalities in the ultrastructure of synaptic boutons in the absence of Atlastin, and aberrant distribution of secretory organelles, accumulation of multivesicular bodies and lysosomes in axons. This suggests that Atlastin is involved in the biogenesis or trafficking of a pool of synaptic vesicles peripheral to the active zone. Taken together, these findings not only provide new insights into the role of Atlastin in the proper organisation of presynaptic terminals, but also validate the Drosophila model for the investigation of complex disease mechanisms.