PRPF3 (pre-mRNA processing factor 3) is an RNA-binding protein that functions as a core component of the U4/U6•U5 tri-snRNP complex, essential for spliceosome assembly and pre-mRNA splicing 1. The protein facilitates spliceosomal complex assembly and catalytic activity through its role in the precatalytic B complex 2. SUMOylation of PRPF3 is required for proper U4/U6•U5 tri-snRNP formation and recruitment to active spliceosomes 1. PRPF3 mutations cause autosomal dominant retinitis pigmentosa (RP), a hereditary form of blindness 3. Pathogenic variants in PRPF3 cluster within the U4/U6 duplex three-way junction region, which normally binds multiple splicing factors including PRPF3 itself, disrupting snRNP biogenesis 2. Variants in RNU4-2 and RNU6 genes that interact with PRPF3 account for up to 1.2% of undiagnosed RP cases 2. Beyond inherited retinal disease, PRPF3 has emerged as a novel oncogene in hepatocellular carcinoma (HCC). Elevated PRPF3 expression promotes HCC cell proliferation and migration, associates with poorer overall and disease-free survival, and correlates with immune infiltration 45. PRPF3 upregulation is transcriptionally regulated by ZNF93 in HCC 5. These findings suggest PRPF3 has dual roles in disease: essential for normal splicing function but pathogenic when dysregulated.