In eukaryotic cells, phosphatidylinositol is subject to differential 
phosphorylation, resulting in the production of seven distinct 
phosphatidylinositol phosphates, often referred to as phosphoinositides (PIs). 
PIs have numerous distinct roles in cellular regulation and membrane 
trafficking. Recently, myotubularin family PI 3-phosphatases have emerged as key 
regulators of phosphatidylinositol 3-phosphate and phosphatidylinositol 
3,5-bisphosphate, two PIs that regulate traffic within the endosomal-lysosomal 
pathway. Mutations in several myotubularin genes lead to myotubular myopathy and 
Charcot-Marie-Tooth peripheral neuropathy. Strikingly, nearly half of the 
members of the human myotubularin family appear to be catalytically inactive. 
Several inactive myotubularins have essential functions in mammals. Recent work 
in mammalian cells and model organisms is shedding light on the roles of 
myotubularins in membrane traffic.