Elizabeth Michele Davies1, Christina Anne Mitchell1 and Harald Alfred Stenmark2,3 1Cancer Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia 2Department of Molecular Cell Biology, Institute for Cancer Research. The Norwegian Radium Hospital, Montebello, N-0379 Oslo, Norway 3Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Montebello, N-0379 Oslo, Norway Correspondence: h.a.stenmarkmedisin.uio.no; michele.daviesmonash.edu

Phosphoinositides (PIs) are phospholipids derived from phosphatidylinositol. PIs are regulated via reversible phosphorylation, which is directed by the opposing actions of PI kinases and phosphatases. PIs constitute a minor fraction of the total cellular lipid pool but play pleiotropic roles in multiple aspects of cell biology. Genetic mutations of PI regulatory enzymes have been identified in rare congenital developmental syndromes, including ciliopathies, and in numerous human diseases, such as cancer and metabolic and neurological disorders. Accordingly, PI regulatory enzymes have been targeted in the design of potential therapeutic interventions for human diseases. Recent advances place PIs as central regulators of membrane dynamics within functionally distinct subcellular compartments. This brief review focuses on the emerging role PIs play in regulating cell signaling within the primary cilium and in directing transfer of molecules at interorganelle membrane contact sites and identifies new roles for PIs in subcellular spaces.