Phosphoinositide turnover is a mechanism of intracellular signaling that involves phosphorylation of the inositol ring to produce signaling molecules that include phosphoinositol (PI)-3-P, PI-3,4-P2, PI-3,4,5-P3, PI-4-P, and PI-4,5-P2. These moleclules function in many signaling pathways to regulate events at cell membranes, such as endocytosis, exocytosis, and cell morphology. Synaptojanin 1 is a phosphoinositide phosphatase that selectively cleaves the 3-, 4-, and 5- phosphates from PIs. Two splice variants of synaptojanin 1 include a 145 kDa form that is found in adult brain, and a 170 kDa that is widely expressed in non- neuronal cells. The 145 kDa form contains a Sac1 domain that has phosphoinositide phosphatase activity, a second phosphatase domain that has only PI-5 phosphatase activity (PI-5), and a proline-rich SH3-binding domain. The 170 kDa form contains these domains, as well as a second SH3-binding consensus sequence. Synaptojanin binds many proteins implicated in endocytosis, including amphiphysins and endophilin. Thus, synaptojanin 1 may regulate endocytosis through modification of the interactions between SH3-domain proteins and PIs.