Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains a pleckstrin homology (PH), Src homology 2 (SH2)-like domains, and proline-rich regions in its C-terminal. STAP-2 belongs to a family of STAP adaptor proteins and plays a crucial role in a variety of cellular signal transduction pathways by interacting with signaling or transcriptional molecules. STAP-2, in particular, regulates both the innate and adaptive immune systems. STAP-2 functionally interacts with signal transducers and activators of transcription 3 (STAT3) and STAT5 in cytokine signaling pathways. In addition, STAP-2 also binds to myeloid differentiation factor 88 (MyD88) and inhibitor (I)κB kinase α/β (IKK-α/β) in Toll-like receptor4 (TLR4) signaling, and enhances the production of inflammatory cytokines in macrophages. More importantly, experiments using STAP-2 deficient mice show that STAP-2 modulates several T-cell functions such as cell motility, survival and death. It is also reported that STAP-2 controls the immunoglobulin E (IgE)-mediated allergy response. This accumulated evidence indicates that adaptor protein STAP-2 is an important modulator of both the innate and adaptive immune systems.