KIRREL3 is a synaptic cell adhesion molecule of the immunoglobulin superfamily that plays critical roles in synapse formation and axonal targeting during neurodevelopment. The protein functions as a homophilic adhesion molecule, with crystal structure studies demonstrating that KIRREL3 forms homodimers through its N-terminal immunoglobulin domains, which is essential for proper axonal coalescence 1. In the hippocampus, KIRREL3 is required for formation of target-specific mossy fiber synapses and mossy fiber filopodia connecting dentate granule and GABA neurons 2. The protein is also crucial for coalescence of vomeronasal sensory neuron axons into glomeruli, with dimerization being necessary for proper glomerular formation 1. KIRREL3 shows extensive expression throughout the adult mouse brain, including hippocampus, cerebral cortex, olfactory bulb, amygdala, thalamus, and cerebellum, exclusively in neurons 2. The gene undergoes complex alternative splicing, generating multiple isoforms including both transmembrane and secreted forms, with splicing patterns varying between mouse and human 3. KIRREL3 interacts with key neuronal proteins including MAP1B and MYO16, which are involved in synaptogenesis and actin cytoskeleton development 4. Clinically, KIRREL3 variants have been implicated in autism spectrum disorder, intellectual disability, and Jacobsen syndrome, though its status as a definitive disease gene requires further validation 5.