Disks large homolog 4

DLG4 (disks large homolog 4) is a postsynaptic scaffolding protein encoded by 724 amino acids that plays a critical role in synaptogenesis and synaptic plasticity (UniProt: P78352). It functions as a structural platform for clustering synaptic proteins, particularly interacting with the cytoplasmic tail of NMDA receptor subunits and potassium channels. DLG4 is required for synaptic plasticity associated with NMDA receptor signaling and regulates AMPA-type glutamate receptor immobilization at the postsynaptic density.

DLG4 is expressed in hippocampal neurons and other neural tissues where it influences the balance of excitatory to inhibitory synapses. The protein cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at synaptic membranes through phosphorylation-dependent mechanisms. DLG4 is associated with intellectual developmental disorder, autosomal dominant 62 (MRD62), a condition characterized by mild to moderately impaired intellectual development.

DLG4 carries SFARI classifications for syndromic autism (SFARI Cat S), indicating curated evidence linking this gene to autism spectrum disorder within syndromic presentations. Its role in fundamental synaptic plasticity and postsynaptic organization positions it as relevant to neurodevelopmental dysfunction.