C9orf78 is a multifunctional protein with roles in both splicing and chromosome 9. In the spliceosome, C9orf78 promotes usage of upstream 3'-splice sites at alternative NAGNAG splice sites and modulates exon inclusion by binding U5 snRNA and displacing WBP4 from SNRNP200 to inhibit its helicase activity 1. Notably, C9orf78 is not required for splicing of shelterin components 2, though its yeast homologue Tls1 regulates shelterin splicing for telomeric heterochromatin assembly 3. Beyond splicing, C9orf78 partially localizes to centromeres and is essential for proper chromosome 9; knockdown causes mitotic defects 2. The protein is growth-regulated, with expression induced by serum stimulation and transcription factors E2F1 and N-Myc 2. Clinically, C9orf78 overexpression occurs in multiple cancer cell lines 3, and it was downregulated in TAF_I-NUP214-positive T-cell acute lymphoblastic leukemia 4. Recently, C9orf78 was identified as a direct target of the miR-34/miR-449 cluster in sinonasal cancers, with dysregulation predicting tumor progression 5. Additionally, C9orf78 interacts with FAM50A to enhance ASNS expression and promote asparagine biosynthesis in breast cancer brain metastasis 6, highlighting its role in cancer-associated metabolic pathways.