Significance Many neurons release neuropeptides as well as classical neurotransmitters. Neuropeptides often regulate neural circuits controlling behaviors such as emotional behaviors. However, how neuropeptide release is regulated is not well-understood. We identified a Drosophila gene, Dstac , that is similar to a vertebrate gene that regulates voltage-dependent calcium channels in skeletal muscles and found that it is active in muscles and a subset of neurons, including motor neurons. Using live imaging, electrophysiology, and genetic manipulations, we found that Dstac localizes to motor synapses with muscles and regulates the voltage response of calcium channels and the release of neuropeptides. Since Stac proteins are found in neurons in the vertebrate CNS, they may also be regulators of neuropeptide release in the vertebrate brain.