Acid-sensing ion channels (ASICs) are members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily and are encoded by five distinct genes, giving rise to seven different subunits. These subunits predominantly assemble into trimeric ion channels that, upon activation by extracellular protons, generate a transient inward current, thereby enhancing cellular excitability. These ion channels, which are activated particularly by extracellular acidification (pH decrease), regulate intracellular ion balance and electrical activity. ASICs exhibit a broad range of tissue distributions and display diverse biophysical characteristics. Moreover, their capacity to form both homomeric and heteromeric trimers adds further complexity to their functional and pharmacological properties. Certain modulators have been identified that lower the proton concentration required for ASIC activation, thereby sensitizing these channels. The roles of ASICs in neurological diseases, pain mechanisms and psychiatric disorders are attracting increasing interest. Substantial evidence from transgenic mouse models and pharmacological investigations indicates that ASICs represent a promising target for therapeutic intervention in various pathological conditions. Further investigation of the molecular mechanisms of ASICs may enable the development of new therapeutic strategies in disease models. This review aims to summarize the current understanding of ASIC function, explore their physiological and pathological roles, discuss mechanisms of modulation, and identify critical gaps in knowledge that warrant further investigation.