Presynaptic active zone is a slightly-electron dense region just beneath the presynaptic plasma membrane, where synaptic vesicles, containing neurotransmitters such as glutamate and GABA, dock, fuse and release the content into the synaptic cleft in a Ca2+-dependent manner. This precisely ordered regulation of neurotransmitter release from the active zone is crucial for normal brain functions such as learning and memory, emotion and consciousness. Currently, a few active zone-specific proteins have been identified and characterized, including Bassoon, Piccolo/Aczonin, RIM1, Munc13-1, CAST/ERC2, and ELKS. These relatively large proteins with significant domain structures have been shown to interact with each other, forming a large macromolecular complex, and play pivotal roles in the structure and function of the presynaptic active zone. In this seminar, I would like to summarize biochemical properties of CAST and ELKS protein family and then show possible physiological significance of CAST/ELKS-mediated protein-protein interactions in excitatory neurotransmitter release. Finally, I also present recent findings about the effect of CAST/ELKS deletion on the integrity and function of specialized active zone in the mouse retina, ribbon synapse.