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Phosphoinositide (PI)–binding domains play critical roles in the intracellular localization of a variety of cell-signaling proteins. The 120–amino acid Phox homology (PX) domain targets proteins to organelle membranes through interactions between two conserved basic motifs within the PX domain and specific PIs. The combination of protein-lipid and protein-protein interactions ensures the proper localization and regulation of PX domain–containing proteins. Upon proper localization, PX domain–containing proteins can then bind to additional proteins and execute their functions in a diverse set of biological pathways, including intracellular protein transport, cell growth and survival, cytoskeletal organization, and neutrophil defense.

With 30,000 to 40,000 genes potentially expressed in the human genome, cells face the difficult task of assembling these gene products into functional complexes and localizing them to …