connexin32

Connexin32, also known as gap junction protein beta-1 and encoded by the GJB1 gene, is a member of the connexin family that forms intercellular channels involved in direct cell-to-cell communication. The protein is widely studied for its role in the peripheral nervous system and liver, and the gene is located on the X chromosome (Xq13.1).

Structurally, connexin32 is a four-transmembrane domain protein with two extracellular loops and cytoplasmic N- and C- termini. Six connexin32 molecules assemble to form a hexameric hemichannel (connexon), and docking of connexons from adjacent cells creates a gap junction channel that permits the diffusion of ions and small metabolites up to about 1 kDa. This arrangement enables coordinated cellular activity across neighboring cells.

Expression of connexin32 is prominent in Schwann cells of the peripheral nervous system and in oligodendrocytes of the central nervous system, where it participates in myelination and metabolic support for axons. It is also present in hepatocytes and other tissues, where gap junctions contribute to tissue homeostasis and coordinated responses.

Clinical significance is primarily linked to mutations in GJB1. Pathogenic variants cause X-linked Charcot–Marie–Tooth disease (CMTX1), a neuropathy characterized by distal weakness and sensory deficits, which can include episodic central nervous system symptoms in some cases. Mutations may disrupt trafficking to the plasma membrane, impair channel formation, or alter gating, leading to loss or alteration of gap junction communication. There is no cure, and management focuses on supportive care and symptom management. Research continues into genotype–phenotype correlations and potential therapeutic approaches to restore connexin32 function.