OTOF encodes otoferlin, a calcium-sensing protein essential for synaptic vesicle exocytosis and neurotransmitter release at cochlear hair cell ribbon synapses 1. The protein functions as a key calcium ion sensor that triggers Ca²⁺-dependent synaptic vesicle-plasma membrane fusion in inner hair cells, enabling sound transduction 2. Mutations in OTOF cause autosomal recessive deafness 9 (DFNB9), characterized by congenital or prelingual severe-to-complete bilateral hearing loss 23. This form of auditory neuropathy represents one of the most common types of genetic hearing loss 4. Recent clinical breakthroughs demonstrate that AAV-mediated OTOF gene therapy can successfully restore hearing in DFNB9 patients, with some achieving near-normal hearing thresholds and speech recognition capabilities 123. In clinical trials, 75% of treated children achieved clinically significant hearing improvement, with some reaching normal hearing sensitivity 3. The therapy shows excellent safety profiles in both preclinical studies and human trials 54. OTOF gene therapy represents a paradigmatic success for genetic hearing loss treatment and serves as a translational model for other forms of hereditary deafness 6.