(A) Different phosphorylated species of PI are enriched in different membrane compartments. PI(3,4,5)P3 (coloured purple) is only made at the plasma membrane when cells are stimulated by either GPCRs or receptor tyrosine kinases (RTKs). PI(4,5)P2 (coloured red) and PI4P (coloured blue) are found at the plasma membranes. PI4P is additionally present at the Golgi. PI3P is present in the endosomal compartment and PI(3,5)P2 is present in multivesicular bodies (MVBs) and lysosomes. (B) Recruitment of proteins by phosphoinositide-binding domains or by patches of positive charge present in proteins by different phosphorylated forms of PI. (C) Activation of AKT by phosphorylation by PDK1 and mTORC2. PIP3 recruits the PH domains of AKT and PDK1 to the plasma membrane bringing the two proteins together. PDK1 phosphorylates AKT. After a second phosphorylation by membrane target of rapamycin complex 2 (mTORC2), AKT is activated and can move away from the membrane to phosphorylate its target proteins (adapted from Figures 1 and 2 from Hammond G.R.V. and Burke J.E. (2020) Current Opinion in Cell Biology, 63:57–67).