Raf kinase inhibitor protein (RKIP) is a cytosolic protein that was initially characterized as a phosphatidylethanolamine-binding protein (PBP) expressed in brain tissue and secreted from testis fluid. In addition, RKIP was identified by yeast two-hybrid screening of human T cell libraries directed at identifying proteins that associate with the BXB kinase domain of the serine/threonine kinase, Raf-1. Subsequent in vitro and in vivo studies indicate that RKIP binds to both the active and inactive forms of Raf-1 and thereby regulates the signaling cascade of the MAP kinase pathway. The specific association of RKIP with kinase-active Raf-1 competitively inhibits the binding and activation of the Raf-1 substrate MEK. RKIP, in turn, affects downstream MAP kinase signaling by decreasing the activation of MEK effector proteins, including ERK1 and ERK2, and the subsequent induction of AP-1 mediated transcription.