GJB6 encodes connexin 30, a gap junction protein essential for intercellular communication through low-molecular-weight material transport between adjacent cells 1. In the cochlea, GJB6 is predominantly expressed in supporting cells, spiral ligament, stria vascularis, and intermediate cells, where it mediates transcellular signaling, metabolic supply, and fluid homeostasis 2. The gene exhibits tissue-specific alternative splicing, with a basal promoter responsive to EGF receptor activation 1. Pathogenic GJB6 variants cause autosomal recessive (DFNB1B) and dominant (DFNA3B) non-syndromic hearing impairment, as well as Clouston-type ectodermal dysplasia. Large deletions like del(GJB6-D13S1830) act as complete loss-of-function variants, nearly abolishing GJB2 expression and causing profound hearing loss exceeding 90 dB SPL with specific cochlear structural abnormalities 3. Mutant GJB6 variants (A88V, G11R) induce keratinocyte apoptosis through caspase-3, -8, and -9 activation, elucidating syndromic dysplasia mechanisms 4. While GJB2 mutations are prevalent in hearing loss populations (up to 40% of autosomal recessive cases), GJB6 point mutations are rarely identified in some geographic populations 56, suggesting ethnic-specific mutation patterns. GJB6 remains a critical therapeutic target for gene therapy interventions in hearing impairment.