Phosphatidylinositol (PtdIns) is a membrane phospholipid composed of 
diacylglycerol and a D-myo-inositol head group. In mammals, the hydroxyl groups 
at the D3, D4 and D5 positions of the inositol ring can be phosphorylated to 
yield seven phosphoinositide derivatives. PtdIns-3,5-bisphosphate 
[PtdIns(3,5)P2] is the most recently discovered species of phosphoinositide that 
is generated by the phosphorylation of PtdIns(3)P at the D5 position by PtdIns 
phosphate kinase and catabolized through the dephosphorylation by myotubularin 
family of phosphatases. Genetic and biochemical analyses of the enzymes 
metabolizing PtdIns(3,5)P2 have revealed that this phospholipid is involved in 
the control of endolysosomal systems and plays crucial roles in various 
mammalian tissues. In this article, we review the current state of knowledge of 
the metabolic/physiological functions of PtdIns(3,5)P2, and describe how 
disruption of these functions may contribute to human diseases.