PI(4)P gets Sac-rificed in the name of endocytic recycling

Phosphoinositide (PI) lipids regulate a wide variety of cellular processes, from cell signaling to cytoskeletal dynamics, by controlling the identity and properties of cellular membranes. A large number of PI kinases and phosphatases restrict the distribution of PI species and give each cellular compartment its own, distinct PI signature. When vesicles are transported from one compartment to another, therefore, their PI composition must be modifi ed accordingly. Two papers by Hsu et al. and Nakatsu et al. reveal that the phosphatase Sac2 promotes endocytic traffi cking by dephospho-rylating PI(4)P (1, 2). Sac2 is one of fi ve vertebrate proteins that contain a Sac1 phosphatase domain.