The neuronal synapse is a specialized cell-cell junction that mediates communication between neurons. The formation of a synapse requires the coordinated activity of signaling molecules that can either promote or restrict synapse number and function. Tight regulation of these signaling molecules are critical to ensure that synapses form in the correct number, time and place during brain development. A number of molecular mechanisms that promote synapse formation have been elucidated, but specific mechanisms that restrict synapse formation are less well understood. The findings presented within this dissertation focus on how a specific Rho guanine nucleotide exchange factor (GEF) Ephexin5 functions to restrict early synaptic development and how perturbations in Ephexin5 signaling may lead to human neurodevelopmental disease.