GJB2 encodes connexin 26, a structural component of gap junctions that form dodecameric channels connecting adjacent cell cytoplasm 12. These channels enable small molecules and ions to diffuse between cells, facilitating intercellular communication 13. In the cochlea, connexin 26 is essential for potassium recycling and ATP release, processes vital for auditory function 4. Mutations in GJB2 are the leading genetic cause of non-syndromic hereditary deafness, with common mutations like 35delG and 235delC disrupting gap junction channel function rather than affecting hair cell survival 5. Gene therapy using AAV-mediated delivery shows promise for restoring hearing in DFNB1 mouse models and large animals 6. Base editing strategies can correct dominant-negative mutations such as R75W, restoring gap junction structure in cochlear supporting cells 7. Beyond its classical role in gap junctions, GJB2 exhibits moonlighting functions in cancer. In hepatocellular carcinoma and lung adenocarcinoma, cytoplasmic GJB2 activates glycolysis through NF-κB and HIF-1α/GLUT-1/PD-L1 pathways, promoting tumor progression and suppressing CD8+ T cell infiltration 89. In ovarian cancer, GJB2 regulates cuproptosis and immune escape, serving as a prognostic biomarker 10.