DLG4 (PSD95, SAP-90) is a membrane-associated guanylate kinase functions in anchoring synaptic proteins and stabilizing synaptic modifications during long-term potentiation, and it is required for synaptic plasticity associated with NMDA receptor signaling. It is primarily found in the post synaptic density of neurons. Changes in DLG4 levels affect the ratio of excitatory/inhibitory synapses in hippocampal neurons, and increases in DLG4 promote synaptic strength, synaptogenesis and multiinnervated spine formation. In aging and in neurodegenerative disorders like Alzheimer’s and Huntington’s disease, downregulation of DLG4 can occur and is associated with changes to hippocampal neuron plasticity and memory deficits. In immunohistochemistry of normal tissue, DLG4 has cytoplasmic positivity in neurons of the central nervous system. References: Journal of Neuroscience. 1996. 16 (4): 1380–1388, PMID: 8778289; Neuron. 2014 Apr 16;82(2):430-43, PMID: 24742464; Brain. 2017 Dec 1;140(12):3252-3268, PMID: 29155979; J Cell Biol. 2008 Dec 15; 183(6): 1115–1127, PMID: 19075115; J Neurophysiol. 2012 Feb 15; 107(4): 1058–1066, PMID: 22114157;