RELN encodes reelin, a large extracellular glycoprotein that plays critical roles in neurodevelopment and brain function. During development, reelin coordinates neuronal migration and layering in the cerebral cortex and cerebellum by binding to lipoprotein receptors VLDLR and LRP8/APOER2, which induces phosphorylation of the intracellular adaptor DAB1 1. This signaling pathway is essential for proper cortical lamination and architectonic pattern formation 1. RELN variants cause a spectrum of neurodevelopmental disorders with variable severity and penetrance. Biallelic loss-of-function variants result in severe lissencephaly with cerebellar hypoplasia, while monoallelic variants can cause frontotemporal lissencephaly, epilepsy, and autism spectrum disorders with incomplete penetrance 2. Some missense variants act through dominant-negative mechanisms, preventing wild-type RELN secretion and causing neuronal migration disorders ranging from pachygyria to polymicrogyria 3. Beyond neurodevelopment, reelin continues to be important postnatally, with LAMP5+RELN+ interneurons migrating into the entorhinal cortex during early childhood 4. Clinically, RELN variants have been associated with psychiatric disorders including schizophrenia and autism 5, and reelin dysfunction may contribute to Alzheimer's disease pathogenesis 6. Additionally, reelin has been identified as a cardioprotective lymphoangiocrine signal important for cardiac development and repair 7.