Prpf8, short for pre-mRNA processing factor 8, is a core component of the spliceosome complex, specifically U4/U6-U5 tri-snRNP. It is integral to the splicing process, ensuring accurate gene transcription and spliceosome assembly, which is crucial for regulating gene expression and protein diversity [3].

Mutations in Prpf8 are associated with various diseases. In retinitis pigmentosa-type 13, the carboxy-terminus of Prpf8, which regulates the RNA helicase Brr2, is a mutation hotspot. Patient-induced pluripotent stem cells carrying the heterozygous Prpf8 c.6926 A > C (p.H2309P) mutation showed retinal-specific endophenotypes, and molecular analyses revealed its role in 5'-splice site selection by spliceosomes [1]. In hepatocellular carcinoma, Prpf8 is overexpressed, increasing tumor aggressiveness by regulating the FAK/AKT pathway via fibronectin 1 splicing [2]. In myeloid malignancies, Prpf8 mutations or hemizygous deletions were identified, leading to missplicing defects, increased proliferative capacity, and poor prognosis [6]. In breast cancer, Prpf8 expression is significantly different between cancer and paracancerous tissues, and high-expression patients have a poor prognosis [4]. Also, heterozygous variants in Prpf8 are associated with neurodevelopmental disorders [5]. In pancreatic cancer, dysregulation of Prpf8 is linked to poor prognosis and malignancy features, making it a candidate actionable therapeutic target [7].

In conclusion, Prpf8 is essential for the accurate splicing of pre-mRNA, and its dysregulation is involved in multiple disease conditions such as retinal diseases, cancers, and neurodevelopmental disorders. Understanding Prpf8's function through model-based research, including gene knockout studies in relevant models, provides insights into disease mechanisms and potential therapeutic strategies.