Required for perception of chronic pain through NMDA receptor signaling. Regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord. Interacts with the cytoplasmic tail of NMDA receptor subunits as well as inward rectifying potassium channels. Involved in regulation of synaptic stability at cholinergic synapses. Part of the postsynaptic protein scaffold of excitatory synapses (By similarity). Interacts through its PDZ domains with NETO1. Interacts with NOS1/nNOS through second PDZ domain (PubMed:8922396). Interacts with KCNJ2/Kir2.1 (via C-terminus) through one of its PDZ domains (By similarity). Interacts with KCNJ4 (By similarity). Interacts with FRMPD4 (via C-terminus) (PubMed:19118189). Interacts with LRFN1 (PubMed:16630835). Interacts with LRFN2 and LRFN4. Interacts with FASLG (By similarity). Interacts with ADAM22 (PubMed:20089912). Interacts with DGKI (via PDZ-binding motif) (PubMed:21119615). Concentrated in soma and postsynaptic density of a subset of neurons (PubMed:11095503). Detected in juxtaparanodal zones in the central nervous system and at nerve terminal plexuses of basket cells in the cerebellum (at protein level) (PubMed:20089912). Brain. High levels in cerebellar Purkinje cells. Expressed in pyramidal cells of the Ammons's horn and granular cells of the dentate gyrus in the hippocampus as well as cerebral cortex and striatum. High levels in dorsal horn of spinal cord. High levels in developing brain and spinal chord, sensory neurons of dorsal root and trigeminal ganglia, myenteric neurons of the intestine as well as in non-neuronal cells of adrenal, thymus and submandibular glands of E15 embryos. Palmitoylation of isoform 1 and isoform 2 is not required for targeting to postsynaptic density. Belongs to the MAGUK family.