SYMPK (symplekin scaffold protein) is a multifunctional scaffold protein located on chromosome 19.3 that plays critical roles in both RNA processing and cellular architecture. Functionally, SYMPK serves as a core component of the mRNA 3' end processing machinery, specifically functioning within the cleavage and polyadenylation specificity factor (CPSF) complex to regulate histone mRNA 3'-end processing and pre-mRNA polyadenylation 1. Beyond its canonical role in 3' end processing, SYMPK exhibits an unanticipated function as a global regulator of alternative splicing. It acts as a cofactor with RBFOX2, NOVA2, and HNRNPA1 RNA-binding proteins to regulate alternative internal exon usage by modulating early intron recognition factors U2AF and U1 snRNP binding 2. SYMPK is also a component of tight junction plaques, contributing to epithelial barrier function 3. Clinically, SYMPK variants show disease associations: a novel SYMPK variant (rs56848936) was identified as significantly associated with colon cancer risk in African Americans, with an odds ratio of 0.61 4. In celiac disease, SYMPK expression is upregulated in active disease but normalizes after gluten-free diet treatment, suggesting reversibility of intestinal epithelial dysfunction 3. Additionally, SYMPK serves as a stable housekeeping gene for gene expression analyses across multiple cancer types and normal tissues 567.