TNF-α activates multiple signaling pathways implicated in endothelial dysfunction including Jun N-terminal kinase (JNK), p38 MAPK and the IκB kinase (IKK) complex that controls activity of activator protein-1 (AP-1), ETS-like-1/3 (ELK1/3), cAMP-response element binding protein (CREB) and nuclear factor kappa B (NF-κB) transcription factors that regulate gene transcription (Figure 1A). The gene discussed is JUN; the disease is endothelial dysfunction.