Model of DP–EB1 interaction with a summary of mutation pathogenicity. (A) When localized to cell–cell contacts, DP provides spatial cues to regulate EB1 and MT organization. Subsequently, MTs can be used for Cx43 trafficking to adjacent gap junctions (model does not include cytoplasmic DP–EB1 interactions, which may also influence MT dynamics). Upon expression of mutations that impair DP–EB1 binding or cause a cytoplasmic shift in the location of DP–EB1 binding, DP is limited in its ability to regulate EB1 and MT association with cortical regions, resulting in a reduction of Cx43 membrane localization and GJIC. (B) Mutations are summarized based on clinical findings and data obtained in this study.