Neuron-specific UBA5 knockdown resulted in reduced NMJ growth and a consistent decrease in synaptic size, which presented as a reduced number of type Ib boutons and increased bouton size in the larval muscles, suggesting that the UFM1 cascade might play a role in the development of NMJs in Drosophila. Our data thus shed light on a role for the UFM1 cascade in neurological diseases. Here, UBA5 is linked to nervous system disorder.