Gap junction beta-2 protein (GJB2) (Cx26)

Connexin 26 (Cx26), encoded by the GJB2 gene, is a critical gap junction protein that facilitates direct intercellular communication by forming channels between adjacent cells. These channels allow the passage of ions, metabolites, and small signaling molecules, playing a vital role in maintaining potassium homeostasis in the inner ear and regulating skin differentiation. Mutations in GJB2 are the leading cause of hereditary non-syndromic hearing loss (DFNB1 and DFNA3) and various syndromic skin disorders like Keratitis-ichthyosis-deafness (KID) syndrome. In oncology, Cx26 is often overexpressed in advanced cancers, where it promotes metastasis and chemoresistance, making it a dual-purpose target for both restorative gene therapies and inhibitory small molecules. Current therapeutic strategies include AAV-mediated gene replacement for loss-of-function mutations and chemical chaperones or hemichannel blockers for gain-of-function variants.

Other names

GJB2CX26DFNA3DFNB1NSRD1PPKHIDKIDBAPSGap junction protein beta 2

The primary mechanisms of action for drugs targeting Connexin 26 include gene replacement therapy to restore functional protein expression in loss-of-function mutations, chemical chaperoning to stabilize and rescue misfolded mutant proteins, and the inhibition of hemichannels or gap junction intercellular communication (GJIC) to prevent pathological ion leakage or tumor metastasis.