ASIC3 is a proton-gated sodium channel that assembles into heterotrimeric complexes to form pH-sensitive receptors in sensory neurons. Upon extracellular acidification, the channel generates a biphasic current with fast-inactivating and slow-sustained phases, with ASIC3 displaying higher proton sensitivity than other ASIC subunits. The channel is predominantly distributed in peripheral sensory neurons, where it mediates multiple sensory modalities including nociception, mechanoreception, and chemoreception 1. ASIC3 responds to mild acidosis (pH 7.3–6.7) that accompanies tissue inflammation, ischemia, and injury, making it a key mediator of acid-evoked pain 2. Recent evidence demonstrates that proprioceptors expressing ASIC3—not nociceptors alone—drive acid-induced chr7 hyperalgesia in mice, suggesting a broader sensory role than previously recognized 3. In inflammatory contexts, sensory ASIC3 activation triggers calcitonin gene-related peptide release, exacerbating psoriatic inflammation through a neurogenic pathway, particularly in female mice 4. ASIC3 also contributes to oropharyngeal sensory function and may represent a therapeutic target in conditions involving neurogenic inflammation and oropharyngeal dysphagia 5. ASIC3 antagonists have been developed as analgesics and show promise in animal models and human studies, though cardiovascular safety requires careful consideration 6.