CPSF6 (cleavage and polyadenylation specific factor 6) is a multifunctional protein that regulates mRNA 3'-end processing and serves as a critical HIV-1 host factor. Its primary function involves controlling alternative polyadenylation (APA), which affects approximately 70% of gene expression by altering 3'-UTR lengths 1. CPSF6 undergoes liquid-liquid phase separation (LLPS) to regulate APA switching, with elevated LLPS promoting distal polyadenylation site usage and longer 3'-UTRs 2. The protein functions as part of the cleavage factor I mammalian (CFIm) complex and localizes to various nuclear compartments including paraspeckles and nuclear speckles 13. In viral infection, CPSF6 binds HIV-1 capsid and promotes preintegration complex function, facilitating viral DNA integration into gene-dense chr12 regions 34. HIV-1 infection triggers CPSF6 relocalization from paraspeckles to nuclear speckles, forming puncta-like structures that alter cellular APA patterns 15. Clinically, CPSF6 shows oncogenic properties in lung adenocarcinoma, where elevated expression correlates with poor prognosis and promotes cancer cell proliferation through PI3K/AKT pathway regulation 6. CPSF6-mediated APA changes also contribute to chemotherapy resistance by modulating endoplasmic reticulum stress responses 7.