This study evaluates the efficiency and specificity of gene therapy using the hair cell-specific Myo15 promoter in treating hearing loss. The researchers compared the expression efficiency and specificity of transgene delivery by AAV-PHP.eB under the Myo15 promoter with that of the ubiquitous CAG promoter. The results showed that the Myo15 promoter initiated efficient expression of the GFP fluorescence reporter in hair cells while minimizing non-specific expression in other inner ear and CNS cell types. Using the Myo15 promoter, they constructed an AAV-mediated therapeutic system with the coding sequence of the Otof gene, which is associated with autosomal recessive deafness (DFNB9). After inner ear injection, they observed significant hearing recovery in Otof−/− mice, highly efficient expression of exogenous otoferlin, and improved exocytosis function of inner hair cells. Overall, the study indicates that gene therapy mediated by the hair cell-specific Myo15 promoter has potential clinical application for treating autosomal recessive deafness and other hereditary hearing losses related to hair cell dysfunction.This study evaluates the efficiency and specificity of gene therapy using the hair cell-specific Myo15 promoter in treating hearing loss. The researchers compared the expression efficiency and specificity of transgene delivery by AAV-PHP.eB under the Myo15 promoter with that of the ubiquitous CAG promoter. The results showed that the Myo15 promoter initiated efficient expression of the GFP fluorescence reporter in hair cells while minimizing non-specific expression in other inner ear and CNS cell types. Using the Myo15 promoter, they constructed an AAV-mediated therapeutic system with the coding sequence of the Otof gene, which is associated with autosomal recessive deafness (DFNB9). After inner ear injection, they observed significant hearing recovery in Otof−/− mice, highly efficient expression of exogenous otoferlin, and improved exocytosis function of inner hair cells. Overall, the study indicates that gene therapy mediated by the hair cell-specific Myo15 promoter has potential clinical application for treating autosomal recessive deafness and other hereditary hearing losses related to hair cell dysfunction.