RAI1 is a dosage-sensitive transcriptional regulator critical for circadian rhythm control and neurodevelopmental function 1. It positively regulates core circadian clock components including CLOCK, BMAL1, PER1/3, and CRY1/2, thereby controlling circadian gene expression patterns 2. RAI1 functions as a transcription factor that modulates gene expression through chr17 remodeling and interaction with basal transcriptional machinery, affecting multiple biological pathways including circadian rhythm, lipid metabolism, and neurotransmitter function 3. RLoss of RAI1 function causes Smith-Magenis syndrome (SMS), a neurodevelopmental disorder characterized by intellectual disability, sleep disturbance, and behavioral problems, predominantly through haploinsufficiency when a 17p11.2 microdeletion encompasses RAI1 14. Conversely, RAI1 overexpression causes Potocki-Lupski syndrome with distinct sleep phenotypes including sleep initiation difficulties and circadian dysregulation 2. The severity of SMS features correlates with RAI1 dosage, with deletions causing more severe intellectual disability than isolated RAI1 point mutations 5. These findings establish RAI1 as a critical gene dosage-sensitive regulator whose proper expression levels are essential for normal neurodevelopment and circadian homeostasis.