An understanding of the molecular mechanism behind the arrhythmic phenotype associated with laminopathies has yet to emerge. A-type lamins have been shown to interact and sequester activated phospho-ERK1/2(pERK1/2) at the nucleus. The gap junction protein connexin43 (Cx43) can be phosphorylated by pERK1/2 on S279/282 (pS279/282), inhibiting intercellular communication. We hypothesized that without A-type lamins, pS279/282 Cx43 will increase due to inappropriate phosphorylation by pERK1/2, resulting in decreased gap junction function. We observed a 1.6-fold increase in pS279/282 Cx43 levels in Lmna−/− mouse embryonic fibroblasts (MEFs) compared to Lmna+/+, and 1.8-fold more pERK1/2 co-precipitated from Lmna−/− MEFs with Cx43 antibodies. We found a 3-fold increase in the fraction of non-nuclear pERK1/2 and a concomitant 2-fold increase in the fraction of pS279/282 Cx43 in Lmna−/− MEFs by immunofluorescence. In an assay of gap junctional function, Lmna−/− MEFs transferred dye to 60% fewer partners compared to Lmna+/+ controls. These results are mirrored in 5–6 week-old Lmna−/− mice compared to their Lmna+/+ littermates as we detect increased pS279/282 Cx43 in gap junctions by immunofluorescence and 1.7-fold increased levels by immunoblot. We conclude that increased pS279/282 Cx43 in the Lmna−/− background results in decreased cell communication and may contribute to the arrhythmic pathology in vivo.