Acid-sensing ion channels (ASICs) are ligand-gated ion channels activated by extracellular proton. To date, six members of ASICs family have been identified. They are widely expressed in the peripheral and central nervous system. Using gene knockout techniques, ASICs are demonstrated to be involved in sensory perception as touch, pain, sour taste, learning and memory as well as some pathological conditions. ASICs can be modulated by neuropeptide, temperature, some metal ions and ischemia-related compounds, integrating multiple extracellular signals to function their roles.