The role of transglutaminase 2 in mediating glial cell function and pathophysiology in the central nervous system

The ubiquitously expressed transglutaminase 2 (TG2) has diverse functions in virtually all cell types, with its role depending not only on cell type, but also on specific subcellular localization. In the central nervous system (CNS) different types of glial cells, such as astrocytes, microglia, and oligodendrocytes and their precursor cells (OPCs), play pivotal supportive functions. This review is focused on what is currently known about the role of TG2 in each type of glial cell, in the context of normal function and pathophysiology. For example, astrocytic TG2 facilitates their migration and proliferation, but hinders their ability to protect neurons after CNS injury. The review also examines the interactions between glial cell types, and how TG2 in one cell type may affect another, as well as implications for specific TG2 populations as therapeutic targets in CNS pathology. •TG2 is expressed in all glia types.•TG2 differentially impacts cellular processes depending on the glia type.•TG2 in glia cells is both beneficial and detrimental depending on the context.