(A) Upstream activating input into distinct classes of PI3Ks and their downstream effector domains/proteins are shown. (B) Subcellular distribution of the distinct PI3K isoform-generated phosphoinositides is shown. The three classes of PI3K specifically generate sub-compartmentally localized 3′-phosphoinositide pools. Only PI(3,4,5)P3 is produced by class I PI3Ks in the plasma membrane, whereas both PI(3,4)P2 and PI(3)P are generated by class II and III PI3Ks, forming distinct cellular pools mainly involved in endo-lysosomal and autophagy pathways.