GJC3 (connexin 31.3/Cx31.3) encodes a gap junction protein expressed primarily in oligodendrocytes that forms hexameric hemichannels assembling into gap junction intercellular channels (GJIChs) for cell-cell communication 1. The protein mediates both electrical and metabolic coupling between cells, with structural studies revealing a ~8 Å pore diameter that selectively transports chloride ions 2. In the central nervous system, oligodendrocytes express GJC3 alongside other connexins (Cx32, Cx47) and form heterotypic channels with astrocyte connexins to facilitate glial communication 1. GJC3 mutations cause nonsyndromic hearing loss through impaired hemichannel function. Two missense mutations (p.R15G and p.L23H) reduce ATP release without affecting membrane trafficking 3, while p.W77S exhibits a dominant negative effect, accumulating in the endoplasmic reticulum and degrading via proteasome/lysosomal pathways 4. Among connexin gene variants, GJC3 mutations associate with flat audiometric configurations in hearing-impaired children 5. Notably, GJC3 expression differs between species: it is confined to mouse myelin but absent from human central nervous system myelin, suggesting species-dependent divergence relevant to translating mouse disease models to humans 6.