PRPF31 (pre-mRNA processing factor 31) is a ubiquitously expressed spliceosomal component essential for pre-mRNA splicing 1. It functions as a critical assembly factor for the U4/U6/U5 tri-snRNP complex, a core building block of the spliceosome 2. This tri-snRNP complex binds directly to regulatory regions of U4 and U6 snRNAs, including sites where RP-associated variants cluster 3. Mutations in PRPF31 cause autosomal dominant retinitis pigmentosa (RP11), a progressive retinal degeneration leading to visual impairment 1. Notably, PRPF31-RP exhibits incomplete penetrance due to haploinsufficiency, where reduced mutant allele expression determines disease manifestation 4. The retina-specific phenotype despite ubiquitous PRPF31 expression remains mechanistically complex 5. Patient-derived retinal organoids and RPE cells reveal that PRPF31 mutations cause selective mis-splicing of genes encoding splicing factors and ciliogenesis proteins, leading to photoreceptor death and RPE dysfunction with impaired phagocytosis and cilia defects 6. PRPF31 mutations also localize to the connecting cilium, establishing unexpected connections between spliceosomal function and ciliary biology 7. Gene augmentation and CRISPR/Cas9 correction successfully rescue defective phenotypes in patient cells, providing therapeutic proof-of-concept 5. PRPF31 variants account for significant RP cases in multiple populations 89.