Genetic and biochemical analysis has revealed that cytoplasmic adapter proteins lacking intrinsic enzymatic activities have crucial roles in leukocyte biology. Despite the growing body of biochemical data to support the importance of 3BP2 in cells of the hematopoietic lineage, a clear picture of its biological function during immune and allergic responses has yet to emerge. Clearly, its exact function in the mechanisms regulating leukocyte activation, proliferation, and survival need to be clarified. This would require identification of specific cellular events and gene patterns regulated by 3BP2 in primary leukocytes. The interaction of 3BP2 with Abl kinases and receptor tyrosine kinases (RTKs) involved in hemapoietic cell activation and development should also be evaluated in the future. 3BP2 may couple to multiple cell surface receptors since the YENX motif that comprises the optimal binding sequence for the 3BP2 SH2 domain is present on diverse receptors and costimulatory molecules. Finally, the involvement of 3BP2 in the rare genetic bone disease cherubism raises the exciting possibility that 3BP2 acts as a “tumor suppressor” downstream from PTKs-coupled receptors in hematopoietic cells.