PRPF8 (pre-mRNA processing factor 8) is a core scaffolding protein of the spliceosome that mediates pre-mRNA splicing in both the major U2-type and minor U12-type spliceosomes 123. PRPF8 functions as a molecular scaffold that positions spliceosomal U2, U5, and U6 snRNAs at splice sites and coordinates ordered assembly of the U4/U6-U5 tri-snRNP complex, enabling catalytic removal of introns and ligation of exons 4. The protein interacts with both 5' and 3' splice sites and regulates the RNA helicase Brr2 to control 5'-splice site selection 5. Pathogenic variants in PRPF8 cause retinitis pigmentosa-13, a retinal degenerative disease characterized by photoreceptor loss and ciliary defects due to disrupted splicing kinetics and aberrant alternative splicing of ciliary and retinal-specific transcripts 56. Recently, heterozygous PRPF8 variants have been associated with neurodevelopmental disorders 7. PRPF8 also controls alternative splicing of PIRH2, an E3 ubiquitin ligase regulating p53, maintaining embryonic stem cell survival 8. Additionally, PRPF8-mediated splicing variants influence colorectal cancer risk through altered PRMT7 isoform expression 9. Mutations in PRPF8 represent a significant genetic cause of non-syndromic retinitis pigmentosa, accounting for disease susceptibility 10.