Tumor suppressors can also act via post-translational modification of IP3Rs. As such, phosphatase and tensin homolog (PTEN) not only counteracts PKB/Akt activity by reducing phosphatidylinositol 3,4,5-trisphosphate (PIP3) levels but also reverses the PKB/Akt-dependent phosphorylation of IP3Rs, particularly at the MAMs where IP3R3 becomes dephosphorylated and de-repressed (117). This evidence concerns the gene ITPR3 and neoplasm.