Cap-independent translation using an internal ribosome entry site instead of the 5'-Cap structure has been discovered in positive-sense RNA viruses and eukaryotic genomes including a subset of gap junction forming connexins genes. With a growing number of mutations found in human connexin genes and studies on genetically modified mouse models mechanisms highlighting the important role of gap junctional communication in multicellular organism it is obvious that mechanism need to be in place to preserve this critical property even under conditions when Cap-mediated translation is scrutinized. To ensure sustained gap junctional communication, rapid initiation of translation of preexisting connexin mRNAs is one possibility, and the presence of internal ribosome entry sites in gap junction genes comply with such a requirement. In this review, we will summarize past and recent findings to build a case for IRES mediated translation as an alternative regulatory pathway facilitating gap junctional communication. This article is part of a Special Issue entitled Electrical Synapses.