The connexin family of proteins form hexameric complexes, called connexons, that facilitate movement of low molecular weight proteins between cells via gap junctions. Connexin proteins share a common topology of four transmembrane ?helical domains, two extracellular loops, a cytoplasmic loop and cytoplasmic N- and C-termini. Many of the key functional differences arise from specific amino acid substitutions in the most highly conserved domains; the transmembrane and extracellular regions. Connexin 31.1, Cx31.1 or Gap junction beta-5 protein, is a 271 amino acid protein that is predominantly expressed in skin with lower expression in testis. Expression of connexin 31.1 is required for normal placental development in mice. Down-regulation of the connexin 31.1 gene correlates with head and neck squamous cell carcinomas (HNSCC) and therefore it may be a potential therapeutic target.