ASIC3 is a proton-gated sodium channel that forms heterotrimeric channels generating biphasic currents with fast-inactivating and slow-sustained phases upon extracellular acidification 1. Predominantly expressed in peripheral sensory neurons, ASIC3 exhibits higher proton sensitivity than other ASIC subunits and mediates a sustained window current during mild acidosis (pH 7.3-6.7) 2. The channel displays high sodium selectivity while permitting other cations 3. ASIC3 functions as a multimodal sensory detector contributing to mechanoreception, acid nociception, and heat nociception 2. In pain signaling, ASIC3 activation in sensory neurons triggers calcitonin gene-related peptide (CGRP) release, promoting nociceptive responses to acidosis in ischemic or inflamed tissues 4. Notably, proprioceptors expressing ASIC3 mediate acidosis-induced chr7 hyperalgesia distinct from nociceptor pathways 5. Beyond pain, ASIC3 has emerging roles in oropharyngeal sensation and swallowing 6, cardiovascular homeostasis through chemoreceptor pH sensitivity in carotid bodies 7, and ocular surface health in dry eye disease 8. ASIC3 antagonism reduces anxiety and enhances insulin sensitivity in knockout models 9, though cardiovascular concerns warrant cautious therapeutic development.