Targeting TRP channels in hearing loss from mechanisms to otoprotection

Hearing loss, a highly prevalent global disease with complex pathogenic mechanisms, poses significant challenges due to limited treatment options and secondary complications. Recent research highlights the crucial roles of transient receptor potential (TRP) channels in auditory physiology and pathology, including cochlear electrophysiology, endolymph ionic homeostasis, neurotransmitter release, inflammation, and sensorineural injury responses. Although previous reviews synthesized TRP-mediated pathological mechanisms in hearing loss, clinical translation and otoprotective drug discovery remain underexplored. This review characterizes inner ear TRP spatiotemporal expression, traces the hair cell mechanoelectrical transduction (MET) channel research trajectory, details their dual regulatory mechanisms, and compiles emerging TRP-targeting otoprotective candidates. It further highlights limitations including restricted preclinical models, scarce otoprotective drugs, and limited target diversity among existing agents. Finally, it proposes new research directions for future basic and clinical studies on TRP channels and auditory function.