Domain structure of major phosphoinositide-metabolizing enzymes. PI phosphatases, such as synaptojanin 1 and oculocerebrorenal syndrome of Lowe (OCRL), harbour clathrin and adaptor protein complex 2 (AP-2) adaptor-binding peptide motifs that target the enzymatic activity to clathrin-coated pits. Rho-GTPase activating protein (RhoGAP) or proline-rich domains (PRDs) might aid in targeting OCRL or synaptojanin 1 to specific intracellular or actin-rich membrane sites. Targeting domains or peptide motifs within PI kinases remain less well defined, although some enzymes, such as PIP(5)K Iγ-p90 or PI(4)K IIβ, contain cargo-like sorting motifs that might associate with AP adaptor complexes. PIK-fyve harbours a phosphatidylinositol 3-phosphate (PI(3)P)-specific binding FYVE domain aiding localization to the endosomal-lysosomal system. DEP, domain present in Disheveled, EGL-10 and Pleckstrin; PI, phosphoinositide; PI(4)K, phosphatidylinositol 4-kinase; PIP(5)K, phosphatidylinositol phosphate 5-kinase; Sac1, yeast suppressor of actin 1; TCP-1, tailless complex polypeptide-1.