Connexin 43 (Cx43), also known as GJA1, is the predominant gap junction protein in vertebrates, encoded by the GJA1 gene. It assembles into hexameric structures in the Golgi apparatus and translocates to the plasma membrane to form gap junction channels, facilitating intercellular communication by allowing the rapid transmission of ions and small molecules between adjacent cells. Cx43 is widely expressed in various tissues, including the heart, where it plays a crucial role in cardiac function and protection against arrhythmias. In addition to its canonical role in gap junction formation, Cx43 has been implicated in non-canonical functions such as cell proliferation, tumor suppression, and stress response. For example, the alternatively translated isoform GJA1-20k protects Cx43 from degradation, stabilizes actin, and mediates ischemic preconditioning. Dysregulation of Cx43 expression is associated with various diseases, including cardiac arrhythmias, cancer, and neurodegenerative disorders.