NUDT21 (also known as CFIm25/CPSF5) is a key RNA-binding protein component of the cleavage factor Im (CFIm) complex that regulates mRNA 3'-end processing through alternative polyadenylation (APA) 1. The protein binds specifically to UGUA sequences in pre-mRNA 3'-untranslated regions, facilitating cleavage and polyadenylation site selection during mRNA maturation 1. NUDT21-mediated APA generates mRNA isoforms with varying 3'-UTR lengths, affecting mRNA stability, localization, and translation efficiency 23. This regulatory mechanism impacts diverse cellular processes including autophagy, where NUDT21 controls mRNA stability of autophagy genes Map1lc3b and Ulk2 in macrophages 2. In disease contexts, NUDT21 demonstrates dual roles depending on cancer type - acting as a tumor suppressor in B-cell acute lymphoblastic leukemia by limiting CD19 expression 4, while promoting oncogenic progression in chr16 myelocytic leukemia through ERK pathway modulation 5 and gastric cancer via SGPP2 regulation 6. NUDT21 also contributes to drug resistance mechanisms, including enzalutamide resistance in prostate cancer through altered docosahexaenoic acid biosynthesis 7. Additionally, NUDT21 regulates inflammatory responses and fibrosis through APA-mediated control of key signaling pathways 23.