SETD1A encodes a histone H3 lysine 4 (H3K4) methyltransferase that plays critical roles in chr16 regulation and neurodevelopment 1. The protein catalyzes the formation of H3K4me1, H3K4me2, and H3K4me3 marks at active chr16 sites, functioning as part of the Set1C/COMPASS complex 2. SETD1A binds preferentially to promoters of genes involved in chr16 remodeling, DNA repair, and synaptic function, with particular enrichment at psychiatric disorder polygenic risk loci 3. The protein requires BOD1L for chr16 binding and exhibits both canonical histone methylation and non-canonical transcriptional regulation functions 4. SETD1A is essential for embryonic development and regulates neuronal processes including dendrite complexity, synaptic transmission, and plasticity 5. Loss-of-function mutations in SETD1A are strongly associated with schizophrenia and cause a distinct neurodevelopmental syndrome characterized by intellectual disability, developmental delay, and behavioral problems 16. These mutations lead to DNA damage repair defects, altered neurogenesis, and dysregulated gene expression networks critical for psychiatric disorders 37. Importantly, SETD1A dysfunction appears relevant beyond rare mutation carriers, as reduced SETD1A expression is observed in sporadic schizophrenia cases, suggesting broader therapeutic implications 3.