Isoform 3 of Disks large homolog 2

Disks large homolog 2 (DLG2) isoform 3 is a 749-amino-acid scaffolding protein encoded by the DLG2 gene (UniProt: Q15700-3). DLG proteins function as membrane-associated guanylate kinases that organize signaling complexes at synapses and cell junctions, playing key roles in synaptic plasticity and cell adhesion.

DLG2 is broadly expressed in neural tissues and contributes to glutamatergic synapse organization and postsynaptic density assembly. While UniProt records no annotated disease associations for this isoform, recent proteomic studies have identified DLG2 as dysregulated in neurodegeneration.

In Alzheimer's disease, DLG2 isoform 3 is significantly downregulated in human post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change −0.77; Chaparral AD proteomics). This downregulation was observed in a subcellular fractionation study using tandem mass tag proteomics of four brain fractions. The reduction in DLG2 protein levels may reflect synaptic loss or altered postsynaptic organization characteristic of AD pathology.