{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:53:14Z","timestamp":1793393594532,"version":"4.5.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>The synaptic adhesion molecule KIRREL3 regulates synapse development in mice and is implicated in human neurological disorders, including autism spectrum disorder, intellectual disability, and Jacobsen syndrome (chromosome 11q deletion syndrome). However, its status as a definitive human disease gene remains unresolved, likely due to the rarity of <jats:italic>KIRREL3<\/jats:italic>-related disorders and significant gaps in understanding its molecular mechanisms. Current knowledge is further fragmented across disparate clinical and basic research reports, often buried in supplemental data. This review synthesizes existing evidence to enable clinicians and scientists to better evaluate <jats:italic>KIRREL3<\/jats:italic> variants as potentially disease causing. We review its conserved role in mediating neuron-to-neuron interactions during axon targeting and synapse formation in mice and how disruptions to these interactions could contribute to neurological pathology in humans. We also discuss how disease-associated variants alter <jats:italic>KIRREL3<\/jats:italic> function. Our analysis underscores the need for integrated studies spanning basic and clinical investigation to validate <jats:italic>KIRREL3<\/jats:italic>\u2019s disease association and advance future interventions for <jats:italic>KIRREL3<\/jats:italic>-related disorders.<\/jats:p>","DOI":"10.3389\/fneur.2025.1662931","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T04:12:46Z","timestamp":1758514366000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of the synapse adhesion molecule Kirrel3 in neurological disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Omar","family":"Shennib","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Raines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda 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