The phosphatidylinositide lipid PI(3,5)P2 is synthesized by an enzyme named Pikfyve or Fab1 in eukaryotes. This enzyme is regulated by at least three conserved adaptor proteins, Vac14, Fig4 and Atg18. Having only been recently uncovered, the role of this enzyme and its lipid products is still under investigation.Recently we have observed that this lipid is synthesized in response to increased nutrient levels in mammalian cells. We also described a loss of mTORC1 function associated with decreases in PI(3,5)P2 levels. In collaboration with several investigators at the University of Michigan we have put forth the hypothesis that direct binding of the Raptor WD40 domain to PI(3,5)P2 is important for lipid regulation of this complex as far back as in budding yeast. Using newly generated genetic tools, we are examining the role of Pikfyve and its regulatory proteins in mice and yeast, focusing on the newly established role of this lipid in nutrient sensing.