INPP5K and muscular dystrophy: Finally, to investigate a causal link between ALR inhibition and muscular dystrophy caused by INPP5K mutations, we evaluated whether the ALR defect due to loss of INPP5K could be restored by expression of either WT INPP5K, a catalytically inactive INPP5K mutant (D310G) that cannot hydrolyze PI(4,5)P2 (35), or INPP5K disease mutants (G140S, I50T, or Y300C), which show reduced PI(4,5)P2 5-phosphatase activity (~70%–85%) (37, 38) (Figure 8, A and B).