ZFC3H1 (zinc finger C3H1-type containing) is a core component of the poly(A) tail exosome targeting (PAXT) complex, which directs polyadenylated RNAs for nuclear degradation by the RNA exosome 1. ZFC3H1 functions as a central link between the exosome cofactor hMTR4 and nuclear poly(A)-binding protein PABPN1, targeting longer and more extensively polyadenylated transcripts compared to other exosome targeting complexes 1. The protein exhibits dual operational modes: it is co-transcriptionally loaded onto RNA precursors in a 'closed' conformation that blocks exosome recruitment, but can transition to an 'open' state that facilitates degradation of shorter RNAs with fewer exons 2. ZFC3H1 also serves as a nuclear RNA retention factor, forming condensates that prevent RNA trafficking to nuclear speckles where RNAs typically gain export competence 34. Additionally, ZFC3H1 participates in quality control mechanisms by interacting with YTHDC1/YTHDC2 to retain misprocessed mRNAs containing intact splice site motifs through m6A modification-dependent pathways 5. Clinically, ZFC3H1 expression correlates with cancer prognosis across multiple tumor types, with altered expression affecting cell viability and metastatic potential 67.