EFTUD2 (elongation factor Tu GTP binding domain containing 2) is a core spliceosomal GTPase that functions as a component of the U5 snRNP and U4/U6-U5 tri-snRNP complex 1. It is essential for pre-mRNA splicing across pre-catalytic, catalytic, and post-catalytic spliceosomal stages, reorganizing the spliceosome complex to promote intron removal from precursor mRNA 2. EFTUD2 also regulates embryonic development and innate immunity by modulating alternative splicing of multiple target genes 2. Mechanistically, EFTUD2 directly interacts with specific mRNA transcripts to regulate their splicing patterns. For example, it modulates Caspase-3 and Aifm1 splicing to generate pro-apoptotic isoforms during cortical development 3, facilitates Kif3a exon skipping in medulloblastoma progression 4, and regulates DDX41 splicing in ovarian cancer 5. EFTUD2 also promotes interferon anti-viral responses by controlling splicing of interferon-stimulated genes including Mx1, OAS1, and PKR 6. Clinical relevance includes mandibulofacial dysostosis with microcephaly (MFDM), where heterozygous EFTUD2 mutations cause craniofacial dysplasia and skeletal anomalies via p53 pathway activation 7. EFTUD2 overexpression promotes progression of hepatocellular carcinoma, colorectal cancer, and ovarian cancer through multiple oncogenic mechanisms, including c-MYC stabilization in chemotherapy resistance 8. High EFTUD2 expression independently predicts poor survival in endometrial cancer 9.