LAUSR

GluD1 and GluD2 receptors belong to the orphan GluD subfamily of ionotropic glutamate receptors (iGluRs). GluDs are classified into iGluRs based on their sequence similarity with other iGluRs. Two decades after GluD were first cloned, they are still considered "orphan" due to lack of knowledge of endogenous ligands that can activate them. Nonetheless, they are crucial for synapse formation, maturation, and maintenance in the CNS and are implicated in multiple neuronal disorders, including schizophrenia, ASD, and depressive disorders. The last decade (2010-2020) has had remarkable revelations that have profoundly changed our understanding of these "orphan" cousins of iGluRs. These significant discoveries include role of GluD receptors in mediating trans-synaptic interactions and their unique non-swapped architecture distinct from other iGluRs. Also prospect of GluD ionotropic activity regulation by direct interaction with metabotropic Glutamate receptors (mGluRs) is exciting. These discoveries will likely drive the field in future providing direction to GluD research.