GRID2 encodes glutamate receptor delta-2 (GluD2), a member of the ionotropic glutamate receptor family that plays crucial roles in cerebellar synaptic organization and development 1. Unlike typical glutamate receptors, GluD2 does not bind glutamate as a primary ligand but instead forms tetrameric receptors essential for synapse organization in cerebellar Purkinje cells 1. The protein is selectively expressed in cerebellar Purkinje cells and mediates synaptogenesis through complex formation with cerebellin proteins 2 1. Mechanistically, certain variants create constitutively active channels, disrupting normal receptor function 1. Disease relevance is significant, as GRID2 mutations cause spinocerebellar ataxia type 18 (SCAR18), an autosomal recessive cerebellar ataxia 2 3. Loss-of-function mutations, including homozygous deletions and duplications, result in cerebellar ataxia, atrophy, developmental delay, and oculomotor abnormalities 2 3. Recently, de novo heterozygous variants have been associated with progressive ataxia and novel findings of alpha-fetoprotein elevation 4. Clinically, GRID2 variants demonstrate genotype-phenotype correlations with intolerant domains identified in both amino terminal and transmembrane regions, suggesting potential therapeutic targets for receptor modulation 1.