NRXN1 is a presynaptic cell-adhesion protein that functions as a critical synaptic organizer in the brain 1. The gene encodes both long α-neurexin and short β-neurexin isoforms through alternative splicing, generating diverse protein variants that establish distinct neurocircuitry 23. NRXN1 regulates synaptic transmission primarily through trans-synaptic complexes with postsynaptic proteins including neuroligins, cerebellins, and GRID1, modulating glutamatergic and GABAergic neurotransmission 2. Cell-type-specific splicing patterns across interneurons, pyramidal neurons, and glia are established during development and remain stable through maturation 3. Heterozygous NRXN1 deletions cause neuropsychiatric disease through both loss-of-function and gain-of-function mechanisms: decreased synaptic activity in glutamatergic neurons contrasts with increased activity in GABAergic neurons 1. Deletions are associated with autism spectrum disorder, schizophrenia, intellectual disability, seizures, and speech/language delays, with reduced penetrance and variable expressivity complicating genetic counseling 45. Genome-wide analysis of 41,321 subjects identified NRXN1 (2p16.3) as a genome-wide significant schizophrenia susceptibility locus with CNV burden enriched for synaptic function genes 5. Precision medicine approaches require stratifying patients by loss-of-function versus gain-of-function mechanisms to tailor therapeutic restoration of NRXN1 isoform repertoires 1.