[7] Through the observation of the crystal structure of neuroligin-1, it was determined that neuroligin-1 forms a protein dimer when two neurexin-1 beta monomers bind to the neuroligin-1's two opposite surfaces.

The interaction of neuroligin and neurexin to form a heterotetramer is monitored by alternatively spliced sites located near the binding interface for Ca2+ in both the neuroligin-1 and the neurexin-1 beta.

[2] Neuroligins have been identified in both vertebrates and invertebrates, including humans, rodents, chickens, Drosophila melanogaster, Caenorhabditis elegans, honeybees and Aplysia.

Neuroligin 2 is mainly concentrated at inhibitory synapses in the CNS, but in mice and humans it may also be expressed in tissues such as the pancreas, lung, endothelia, uterus and colon.

Neuroligin 3 is expressed in CNS neurons, as well as a variety of glial cells in mice and rats and the brain, heart, skeletal muscle, placenta and pancreas in humans.

[10] Neuroligin mRNA are present in human endothelial cells from large blood vessels [12] and in Dorsal Root Ganglions.

[13] Alternative splicing, a modification that occurs after transcription of mRNA, regulates neuroligins’ binding selectivity for α- or β-neurexins as well as the function of synapses.

[14] Neurexin and neuroligin work together to gather and maintain the cytoskeleton components needed to localize synaptic vesicles.

[10] However, evidence suggests that additional adhesion molecules, such as immunoglobulin-domain and cadherin family proteins, mediate the initial contact between the axons and dendrites for a synapse.

[14] In addition to the selectivity of splice variants, the levels of neuroligins, neurexins, and other interacting proteins present on the pre- and postsynaptic membranes influence the differentiation and balance of synapses.

Inhibitory synapses decrease probability of firing an action potential in the postsynaptic neuron and are often GABAergic, in which the neurotransmitter GABA is released.

[17] The small amount of mutant protein that reached the cell membrane demonstrated diminished binding activity for neurexin-1, consistent with a loss of function.

[18] The mutant gene has been cloned and was introduced into mice, resulting in impaired social interactions, enhanced spatial learning abilities and increased inhibitory synaptic transmission.

A frame shift mutation 1186T has been found to cause an early stop codon and premature protein truncation.

[20] Other mutations of NLGN4 found in relation to autism spectrum disorders include a 2-bp deletion, 1253delAG, in the NLGN4 gene, which causes a frameshift and a premature stop codon.