SNRNP200 is a core U5 snRNP helicase that catalyzes ATP-dependent unwinding of U4/U6 RNA duplexes, an essential step in spliceosome assembly and pre-mRNA splicing 1. It functions throughout the spliceosome life cycle, participating in precatalytic, catalytic, and postcatalytic complexes while mediating dynamic RNA-RNA interactions 234. Beyond splicing, SNRNP200 serves dual roles: its Sec63 domain binds viral RNA and interacts with TBK1 to promote IRF3-mediated antiviral responses 5, and it associates with stress granule proteins during cellular stress 6. Pathogenic SNRNP200 variants cause retinitis pigmentosa (RP33), a progressive rod-cone dystrophy affecting retinal function 7. Two RP-linked mutations (S1087L and R1090L) impair the protein's helicase activity by altering its interaction with U4 and U6 snRNAs, with broader binding profiles suggesting defective snRNA unwinding 8. Notably, SNRNP200 demonstrates tissue-specific disease manifestation despite ubiquitous spliceosomal expression 9. A large clinical cohort shows median BCVA preservation until the 6th decade with annual decline of 0.021 LogMAR 7, indicating slowly progressive retinal degeneration. Recent findings reveal SNRNP200 surface expression on AML cells as a potential immunotherapeutic target 10, while genetic studies identify SNRNP200 loss-of-function variants as neurological resilience modifiers in Niemann-Pick C disease 11.