Signal-transducing adaptor protein family of proteins (STAPs), which currently contains two members, are proposed to be adaptor molecules because of their pleckstrin homology (PH) and Src-homology 2 (SH2)-like domains. STAP-1 has been shown to interact with STAT5 and the tyrosine kinase Tec. With regard to STAP-2/BKS functions, immunoprecipitation experiments and intracellular stainings revealed STAP-2/BKS binds STAT5 in several types of cells. Mutational studies revealed that the PH- and SH2-like domains of STAP-2/BKS interacted with the C-terminal region of STAT5. STAP-2/BKS and STAT5 were found to constitutively co-localize in the cytoplasm of resting cells, but STAP-2/BKS was found to dissociate upon STAT5 phosphorylation, suggesting a role in regulating signaling of STAT5. The physiological role of these interactions is not fully understood, but in studies of overexpression of STAP-2/BKS, cytokine-induced tyrosine phosphorylation and transcriptional activation of STAT5 was diminished. In addition, thymocytes from STAP-2/BKS-deficient mice showed the enhanced interleukin-2-dependent cell growth. Taken together, STAP-2/BKS is an additional modulator of STAT5-mediated signaling.