Recent advances in the human genetics of neurodevelopmental disorders (particularly, autism spectrum disorders) have identified recurrent mutations in genes encoding a variety of synaptic genes, including synaptic adhesion molecules. Trans-synaptic adhesion molecules and their ligands instruct and specify the properties of synapses and neural circuit, emerging as key synapse organizers. Neurexins and neuroligins are arguably most extensively studied pair of synapse organizers. Neurexins bind to multiple postsynaptic ligands, including LRRTMs and neuroligins. Neuroligins also bind to MDGA family of GPI-anchored proteins for negatively regulating synapse development. My talk is based on two hypotheses: first, that multiple trans-synaptic adhesion molecules and their associated proteins (i.e. synapse organizers) are central to synapse formation and function, and second that defective trans-synaptic adhesion signaling manifests in the forms of various brain diseases. I will describe some of our recent studies on how neurexins, neuroligins, and MDGAs are involved in shaping synapse properties, and discuss how these mechanisms may contribute to our understanding pathophysiology against neurodevelopmental disorders, such as autism spectrum disorders.