Like the type I interferons (IFNs), the recently discovered cytokine IFN-lambda displays antiviral, antiproliferative, and proapoptotic activities, mediated by a heterodimeric IFN-lambda receptor complex composed of a unique IFN-lambda R1 chain and the IL-10R2 chain. However, the molecular mechanism of the IFN-lambda-regulated pathway remains unclear. In this study, we newly identified RAN-binding protein M (RanBPM) as a binding partner of IFN-lambda R1. The interaction between RanBPM and IFN-lambda R1 was identified with a glutathione S-transferase pull-down assay and coimmunoprecipitation experiments. IFN-lambda 1 stimulates this interaction and affects the cellular distribution of RanBPM. However, the interaction between RanBPM and IFN-lambda R1 does not correlate with their conserved TRAF6-binding sites. Furthermore, we also found that RanBPM is a scaffolding protein with a modulatory function that regulates the activities of IFN-stimulated response elements. Therefore, RanBPM plays a novel role in the IFN-lambda-regulated signaling pathway.