Isoform 9 of Disks large homolog 1

DLG1 (disks large homolog 1) is a membrane-associated scaffolding protein that functions as a key component of the postsynaptic density and cell junction complexes (UniProt: Q12959-9). It belongs to the MAGUK family of proteins and plays important roles in organizing synaptic signaling through protein–protein interactions via its PDZ and SH3 domains. DLG1 localizes predominantly to synaptic and epithelial compartments where it stabilizes and clusters ion channels and receptors.

DLG1 is widely expressed in neural tissues and has established roles in synaptic plasticity, neuronal development, and epithelial cell architecture. In neuronal contexts, it functions as a critical adapter linking transmembrane receptors to downstream cytoplasmic signaling pathways. Mutations and dysregulation of DLG1 have been implicated in developmental and neuropsychiatric conditions (UniProt: Q12959-9).

In Alzheimer's disease, isoform 9 of DLG1 is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC: −0.34; Chaparral AD proteomics). This down-regulation was detected across 2 of 4 subcellular fractions in a TMT-labeled, data-dependent acquisition mass spectrometry study of human brain. The reduced levels of this synaptic scaffolding protein may contribute to synapse loss and cognitive decline characteristic of AD pathology.