MAGI2 is a member in the Membrane-associated guanylate kinase with an inverted arrangement of protein-protein interaction domains (MAGI) family, and includes two additional family members, MAGI1 and MAGI3¹.

MAGI proteins are essential for efficient cell signaling as they function as scaffolds for assembling cell adhesion molecules, receptors and signaling molecules and linking them to the cytoskeleton².

MAGI2 has a guanylate kinase, 2 WW, and 6 PDZ domains (PDZ0-PDZ5). It interacts with cytoskeleton-associated proteins: guanylate-kinase-associated protein (GKAP), Postsynaptic density-95 (PSD-95)/synapse-associated protein 90 (SAP90), Stargazin/transmembrane AMPAR regulatory proteins (TARPs). MAGI2 also interacts with N-methyl-D-aspartate (NMDA) receptors, δ2 Glutamate receptor, β1AR, VPAC1, Brain-specific angiogenesis inhibitor-1, Activin Type II receptors, Neuroligins, β-Dystroglycan, Dendrite arborization and synapse maturation 1 (Dasm1)/IgSF9b, Nectins and Nephrin receptors and cell adhesion proteins, respectively^1,3.

MAGI2 expression is almost exclusively in brain, deletion of MAGI2 causes infantile spasm and increased cognitive impairment in schizophrenia patients⁴.

In non-neuronal tissues, MAGI2 enhances the ability of PTEN to suppress Akt activation in the PI3-kinase/Akt pathway. PTEN binds to MAGI2 through the PDZ domains, thus enhancing PTEN stability and improves the efficiency of PTEN signalling, allowing for efficient tumor suppression by PTEN^1,5.