CDC40 is a core component of the activated spliceosome required for pre-mRNA splicing, specifically participating in the second step of the splicing reaction 1. The protein contains multiple WD repeats and functions as a spliceosome-associated factor that co-precipitates splicing intermediates 1. Beyond splicing, CDC40 plays an important role in embryonic brain development through mechanisms independent of proline isomerization 2. CDC40 depletion induces widespread splicing defects, including intron retention in cell cycle regulatory genes like CDCA5, leading to cell cycle arrest, growth inhibition, and apoptosis 3. The protein may have a more direct role in nonsense-mediated mRNA decay (NMD) regulation beyond indirect effects of spliceosome dysfunction 4. Clinically, CDC40 is essential for lung cancer cell survival and represents a potential therapeutic target 3. CDC40 is regulated post-transcriptionally by multiple microRNAs (miR-422a, miR-378, miR-1269b), and dysregulation contributes to gastric and colorectal cancer progression 5 6. Mutations in CDC40 are associated with pontocerebellar hypoplasia 15 and have been identified in patients with mitochondrial disorders 7, suggesting broader roles in human disease beyond splicing defects.