Engagement of the interleukin‐1 (IL1) and Toll receptors, which are part of the innate immune system, facilitates activation of the transcription factors NF‐κB, Elk‐1 and AP‐1. Pellino1 and Pellino2 have recently been shown to be intermediates in the pathway leading to activation of NF‐κB. Here we demonstrate for the first time that human Pellino2 interacts with TRAF6 (tumor necrosis factor receptor associated factor 6) and that both Pellino1 and Pellino2 also interact with TAK1 (transforming growth factor‐β activated kinase 1). We also show that Pellino2, but not Pellino1, can activate the mitogen activated protein kinase pathway leading to activation of AP‐1 and Elk‐1. These observations suggest a role for the Pellino proteins in the IL1/Toll signaling cascades as scaffold proteins that may regulate signaling branch‐points.