PI3K/AKT activation stabilizes G6PD, the rate-limiting enzyme of the PPP, by inhibiting the E3 ligase tripartite motif-containing protein 21 (TIRM21) and promotes the PPP, which in turn supports AKT activation and additionally enables cancer metabolic reprogramming by suppressing the expression of the AKT inactivator pleckstrin homology-like domain family A member 3 (PHLDA3) [53]. Here, AKT1 is linked to cancer.