Defective synaptic transmission at the neuromuscular junction (NMJ) contributes to motor neuron disease. However, our understanding of the regulation of synaptic transmission remains incomplete. Through bioinformatics analysis, we identified 420 candidate synaptic regulators that may play an essential role in development or function of the NMJ. Using RNAi we specifically knocked down each gene in the fruit fly motor neuron and identified animals with defects in NMJ development or motor function over their lifespan.  In parallel, we are investigating genes that when targeted can suppress a MND phenotype (expression of TDP-43 in motor neurons) in the fly. So far we have identified 100 new synaptic genes that have an essential role in motor neuron function. Gene ontology analysis of these hits suggests associations with microtubule organisation and regulation of secretion. We are continuing our gene identification efforts and will further examine candidate genes for synaptic development, synaptic function, and an ability to suppress MND pathology in vivo.