The role of cell adhesion molecule IgSF9b at the inhibitory synapse and psychiatric disease

Understanding perturbations in synaptic function between health and disease states is crucial to the treatment of neuropsychiatric illness. While genome-wide association studies have identified several genetic loci implicated in synaptic dysfunction in disorders such as autism and schizophrenia, many have not been rigorously characterized. Here, we highlight immunoglobulin superfamily member 9b (IgSF9b), a cell adhesion molecule thought to localize exclusively to inhibitory synapses in the brain. While both pre-clinical and clinical studies suggest its association with psychiatric diseases, our understanding of IgSF9b in synaptic maintenance, neural circuits, and behavioral phenotypes remains rudimentary. Moreover, these functions wield undiscovered influences on neurodevelopment. This review evaluates current literature and publicly available gene expression databases to explore the implications of IgSF9b dysfunction in rodents and humans. Through a focused analysis of one high-risk gene locus, we identify areas requiring further investigation and unearth clues related to broader mechanisms contributing to the synaptic etiology of psychiatric disorders.