ADGRB2 (adhesion G protein-coupled receptor B2), also known as BAI2, is an orphan GPCR involved in cell adhesion and cell-cell interactions 1. The receptor activates NFAT-signaling pathway through the G-protein GNAZ, functioning as a transmembrane signaling receptor in multiple physiological contexts 2. ADGRB2 is involved in negative regulation of angiogenesis and shows expression in the peripheral nervous system and synaptic regions. Disease relevance: ADGRB2 has emerged as a novel candidate gene in neuropsychiatric conditions. Large-scale exome studies identified ADGRB2 as associated with adult cognitive function through rare protein-coding variants with large effects 3. Additionally, ADGRB2 was discovered among six newly identified genes associated with depressive symptoms in a UK Biobank exome-wide association study of 296,199 participants 4, with immune response pathways implicated in this association. Similarly, rare variants in ADGRB2 showed significant association with neuroticism in 394,005 UK-based individuals 5. Clinical significance: ADGRB2 appears as a candidate disease gene with potential relevance to neurodevelopmental and psychiatric disorders 6. Its involvement in both cognitive function and affective disorders suggests therapeutic potential as a target for neuropsychiatric interventions, though mechanistic studies are needed to clarify its specific contributions to these conditions.