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Connexin 26 in Hearing Health and Disease: StructuralFoundations, Mutation Mechanisms, and Therapeutic Perspectives

Year: 2026

Type: article

Abstract: Mutations in gap junction protein β-2 (GJB2), encoding Connexin 26 (Cx26), are the most common genetic cause of hearing loss, responsible for up to 50% of inherited non-syndromic cases worldwide. This review covers Cx26 from three perspectives: protein structure, mutant disease mechanisms, and treatment approaches. Structurally, 12 Cx26 subunits assemble into a gap junction channel connecting neighboring cells, enabling exchange of ions and signaling molecules; activity is regulated by calcium, pH, and CO2. In the cochlea, Cx26 channels are required for the development of sound-sensing hair cells, maintenance of the electrical gradient needed for hearing, and energy supply during sound processing. GJB2 mutations cause hearing loss through three mechanisms, complete loss of functional protein, failure of channel assembly or membrane delivery, and abnormal channel gating, that damage cochlear cells. Severity ranges from profound congenital deafness to gradual decline, depending on which mutations are inherited. Gene therapy, genome editing, and pharmacological approaches are under investigation; cochlear implantation remains the current standard of care.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27114831

Authors: Weihua Qiu, Kaelah Schneider, Youzhong Guo

Institution: Virginia Commonwealth University

Language: English

Topic: Hearing, Cochlea, Tinnitus, Genetics

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499