SNW1 (SNW domain containing 1) is a multifunctional spliceosomal protein and transcriptional coactivator critical for both RNA processing and gene regulation. Primary function: SNW1 functions as a core spliceosomal component essential for pre-mRNA splicing 1 and as a transcriptional coactivator regulating NF-κB and Notch signaling pathways 23. Mechanism: SNW1 mediates splicing of genes encoding cohesion proteins (sororin and APC2) required for sister chr14 cohesion 4. In transcriptional regulation, SNW1 detaches from splicing complexes upon pathway activation and binds transcriptional elongation factors like p-TEFb to facilitate target gene expression 2. SNW1 activity is regulated by post-translational O-GlcNAcylation, which modulates its interaction with NF-κB 5. Disease relevance: Heterozygous SNW1 mutations cause primary microcephaly through defective splicing and impaired neural stem cell proliferation 1. SNW1 is upregulated in neuroblastoma and associated with poor prognosis 3. SNW1 dysregulation contributes to gestational diabetes pathophysiology through altered glucose metabolism and insulin signaling 6. In glioblastoma, SNW1 recruitment to super-enhancers drives pro-inflammatory signaling 7. Clinical significance: SNW1 represents a potential therapeutic target for neurodevelopmental disorders, cancer, and metabolic diseases, with therapeutic modulation via kinase inhibitors or small molecule inhibitors showing promise 176.