CSTF3 (cleavage stimulation factor subunit 3) is a core component of the mammalian mRNA 3'-end processing machinery, functioning as a critical regulator of alternative polyadenylation (APA). CSTF3 is one of multiple factors required for polyadenylation and 3'-end cleavage of pre-mRNAs 1, operating within the mRNA cleavage stimulating factor complex in the nucleus. Mechanistically, CSTF3 regulates mRNA stability and protein expression through APA-mediated control of 3' UTR length. CSTF3 binding downstream of polyadenylation sites promotes proximal site usage, generating shorter 3' UTRs that are more stable and less susceptible to posttranscriptional regulatory elements 2. This APA regulation affects diverse target genes including FSP1, NEAT1, Mmp9, and numerous others across the genome 134. CSTF3 dysfunction is implicated in multiple cancers. Elevated CSTF3 expression promotes platinum resistance in ovarian cancer through NEAT1 isoform switching 3, drives tumorigenesis in triple-negative breast cancer 2, and contributes to advanced prostate cancer progression through intron retention in pre-mRNA processing genes 5. CSTF3 also regulates ferroptosis suppression in lung cancer and may serve as a diagnostic biomarker for inflammatory diseases 16. CSTF3 expression is responsive to integrin signaling, linking it to wound healing and epithelial remodeling 4.