PRP4K is a serine/threonine kinase essential for multiple cellular processes centered on pre-mRNA splicing and signaling regulation. Primary Function: PRP4K functions as a critical component of spliceosomal assembly, directly phosphorylating PRPF6 and PRPF31 components of the U4/U6-U5 tri-snRNP complex to facilitate formation of the functional spliceosome B complex 1. Beyond splicing, PRP4K regulates Hippo pathway signaling by phosphorylating nuclear YAP1 and WWTR1/TAZ, promoting their nuclear exclusion to control tissue growth 2. Mechanism: PRP4K associates with U5 snRNP and NCOR1 deacetylase complexes, coordinating pre-mRNA splicing with chr6-mediated transcriptional regulation 3. Notably, PRP4K regulates splicing of CHMP4B/vps32, ESCRT-III genes controlling autophagosome-lysosome fusion, representing an evolutionarily conserved splicing circuit 4. Disease Relevance: Reduced PRP4K expression functions as a haploinsufficient tumor suppressor, associated with aggressive breast and ovarian cancer phenotypes, taxane resistance, and increased cell migration/invasion 5, 6. Clinical Significance: High PRP4K expression correlates with improved overall survival in taxane-treated ovarian cancer patients and breast cancer 5. PRP4K inhibition through competing proteins like YAPer-ORF promotes aberrant cell growth in cancer models, suggesting therapeutic targeting potential 7.