The lipid phosphatase Sac1 was identified more than 25 years ago in a yeast genetic screen. Since then, investigators have learned much about its roles in the cell. In this review, we present our current understanding of Sac1 structure, regulation and function, and we describe how Sac1—as a phosphatidylinositol 4‐phosphatase—plays multifaceted roles in membrane homeostasis, vesicular and nonvesicular transport, cell signaling, development and disease. The lipid phosphatase Sac1 dephosphorylates phosphatidylinositol 4‐phosphate (PI4P), thereby holding levels of this crucial membrane signaling molecule in check. Sac1 regulates multiple cellular processes, including cytoskeletal organization, membrane trafficking and cell signaling. Here, we review the structure and regulation of Sac1, its roles in cell signaling and development and its links to health and disease. Remarkably, many of the diverse roles attributed to Sac1 can be explained by the recent discovery of its requirement at membrane contact sites, where its consumption of PI4P is proposed to drive interorganelle transfer of other cellular lipids, thereby promoting normal lipid homeostasis within cells.