ASIC4 is an acid-sensing ion channel subunit that functions distinctly from other ASIC family members. Unlike ASIC1a, ASIC1b, ASIC2a, and ASIC3, ASIC4 does not form functional homomeric channels activated by protons 1, and instead may form pH-gated heterotrimeric sodium channels with other ASIC subunits 2. ASIC4 is widely distributed throughout the central nervous system, with expression in interneurons, oligodendrocyte precursor cells, and cerebellar granule cells 3. Notably, ASIC4 predominantly localizes to early endosome-related compartments upon heterologous expression, suggesting a role distinct from plasma membrane ion conduction 1. Functionally, ASIC4 plays a critical role in regulating innate fear and anxiety responses. ASIC4-knockout mice display increased freezing to predator odor and elevated anxiety-like behavior in behavioral tests, suggesting ASIC4 may modulate fear by counteracting ASIC1a activity 3. ASIC4 expression in the hippocampus is regulated by follistatin and is essential for learning and synaptic plasticity, including long-term potentiation 4. Additionally, ASIC4 is expressed in lactotroph cells of the anterior pituitary 5. While ASIC4's exact gating mechanisms remain unclear 6, its roles in anxiety, fear processing, and cognitive function represent important distinctions from other ASIC family members.