ADGRL3 (adhesion G protein-coupled receptor L3), also known as latrophilin-3, is an orphan adhesion GPCR that mediates synapse specificity and glutamatergic synapse formation 1. The receptor couples to Gs proteins to activate adenylate cyclase signaling and undergoes liquid-liquid phase transitions to associate with PDZ-containing proteins like SHANK3 and DLG4, directing synapse assembly. Functionally, ADGRL3 requires coincident binding of both FLRTs and teneurins to promote excitatory synapse formation at specific dendritic locations, with latrophilin-3 selectively directing formation of Schaffer-collateral synapses in hippocampal CA1 neurons 2. ADGRL3 shows peak expression early in neurodevelopment, localizing primarily to growth cone-like structures in glutamatergic neurons 3. ADGRL3 expression in the trigeminovascular system associates with migraine pathophysiology 4. Clinically, ADGRL3 genetic variants are significantly associated with ADHD susceptibility, particularly in childhood 5. Meta-analysis confirms associations with multiple polymorphisms (rs6551665, rs1947274, rs2345039) predominantly in pediatric ADHD populations 5. The rs1397547 SNP associates with altered ADGRL3 transcription and dysregulated glutamatergic neuron development 3, mechanistically linking genetic variation to neurodevelopmental dysfunction 6. These findings establish ADGRL3 as a key regulator of synaptic development with important implications for neurodevelopmental and neurological disorders.