Epithelium is the interface between the body and world, and thereby the forefront of sensing and fighting with foreign substances. There are epithelial cells that are responsive to chemical substances and communicate with afferent nerves to evoke biological reactions. However, transduction and neurotransmission mechanisms of these sensory epithelial cells seem diverse and are poorly understood. We previously identified an unprecedented chemical synapse in taste bud cells which are a type of sensory epithelial cells that mediate gustation. Remarkably, taste bud cells employ an ion channel pore as the conduit for neurotransmitter release. As chemical neurotransmission was supposed to be mediated solely by exocytosis, we termed this unique chemical neurotransmission machinery “channel synapse”. Where else does the synapse exist and function outside the tongue? Here, we generated a reporter mouse for Calhm1 and 3, core components of the channel synapse, screened over 40 organs for reporter expression, and revealed extra-oral distribution of cells expressing Calhm1 and 3. In one of those CALHM1/3⁺ tissues, we genetically, anatomically, and functionally identified the presence of channel synapses and its physiological roles. The discovery, structure and function of the CALHM channel synapse will be discussed.