Gap junction beta-2 protein (GJB2) (GJB2)

Gap junction beta-2 protein (GJB2), also known as Connexin 26 (Cx26), is a vital transmembrane protein that forms gap junctions and hemichannels essential for intercellular communication in the inner ear and skin [4, 12, 19]. In the cochlea, Cx26 is primarily responsible for potassium ion recycling, a physiological process that maintains the endocochlear potential required for sensory hair cells to convert sound waves into electrical signals [4, 11, 15]. Mutations in the GJB2 gene are the most common cause of congenital nonsyndromic hearing loss worldwide, accounting for approximately 50% of autosomal recessive cases [1, 10, 12]. Beyond hearing, GJB2 plays a role in epidermal homeostasis, and specific mutations can lead to syndromic skin disorders such as Vohwinkel syndrome and Keratitis-ichthyosis-deafness (KID) syndrome [10, 12, 19]. Therapeutic development is currently focused on AAV-mediated gene replacement therapies, such as SENS-601 and OTO-825, which aim to restore functional Cx26 expression in cochlear supporting cells to treat genetic deafness [1, 11, 16]. While no drugs are currently approved, GJB2 remains a high-priority target for precision medicine in otology and dermatology [1, 9, 13].

Other names

Connexin 26Cx26DFNB1NSRD1Gap junction beta-2

Gene replacement therapy (AAV-mediated delivery of functional GJB2 gene)