GJE1 encodes connexin 23 (Cx23), an atypical gap junction protein that differs functionally from other connexins. Unlike conventional connexins, Cx23 contains only 4 cysteine residues in its extracellular loops instead of the typical 6, and does not form functional gap junction channels between cells 1. Instead, Cx23 mediates calcium-independent ATP release through hemichannel activity, suggesting it functions more like pannexin channels than traditional gap junctions 1. The protein is specifically expressed in oligodendrocytes within the CNS, where it does not colocalize with other connexins such as Cx26, Cx30, Cx32, Cx43, or Cx47 2. Notably, the GJE1 gene appears to be inactivated in primates, with all analyzed primate genomes containing stop codons and no detectable transcripts in human tissues 1. Genetic variants in GJE1 have been associated with bortezomib-induced peripheral neuropathy in cancer patients, potentially through effects on Schwann cell coupling 3. The gene has also been investigated as a candidate for hereditary sensorineural hearing loss and erythrokeratodermia variabilis, though its role in these conditions remains unclear 45.