Phosphoinositides, derived from phosphorylation of phosphatidylinositol at one or more positions on the inositol ring, are minor but significant lipids in eukaryotic cell membranes. Phosphatidylinositol (4,5)-bisphosphate (PIP2) is the most abundant phosphoinositide and is concentrated in the plasma membrane. PIP2 functions in cell motility, adhesion, exocytosis, and endocytosis, among other processes. Model membrane studies have shown that PIP2 can form electrostatic-based clusters with Ca++ and with basic peptides. Recent studies in cells have shown that PIP2 can co-cluster with polybasic peptides present in cellular proteins as well, with important functional consequences.