Neuroligin-3 (NLGN3)

Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion molecule crucial for synaptogenesis, synaptic maintenance, and plasticity in the central nervous system[1][2]. Unlike other neuroligins, NLGN3 localizes to both excitatory and inhibitory synapses, regulating the balance between their transmission[2]. NLGN3 forms a trans-synaptic bridge by binding presynaptic neurexin proteins, stabilizing synaptic contacts, and orchestrating postsynaptic protein complexes essential for fast and efficient neurotransmission[1]. Structurally, NLGN3 is a single-pass transmembrane protein with a large extracellular α/β-hydrolase fold domain for neurexin binding, a transmembrane segment, and a short intracellular domain that links to scaffolding and signaling proteins in the postsynaptic density[1]. Dysfunction of NLGN3 due to genetic mutations, such as R451C, is implicated in neurodevelopmental disorders—notably autism spectrum disorder—by disturbing synaptic structure, pruning, or excitatory/inhibitory balance[1][2][3]. NLGN3 is also robustly expressed in certain glia, where its non-synaptic functions may involve regulation of gene expression rather than direct synapse formation[3].

Other names

Neuroligin 3NLGN3KIAA1480NL3HNL3ASPGX1AUTSX1Gliotactin homolog

Not applicable (no approved drugs directly targeting this protein). For future strategies: disruption or modulation of NLGN3 function could alter synaptic adhesion or balance of excitatory/inhibitory signaling[1][2].