TENT4B (terminal nucleotidyltransferase 4B) is a non-canonical RNA polymerase that catalyzes the addition of ATP and GTP to mRNA 3' poly(A) tails, generating mixed adenosine-guanosine tails that protect transcripts from rapid deadenylation 1. This mixed tailing mechanism shields mRNA from the CCR4-NOT deadenylase complex, stabilizing mRNAs and maintaining their cellular abundance 1. TENT4B functions as a catalytic subunit in TRAMP-like complexes involved in post-transcriptional quality control, catalyzing short oligo(A) tail addition to nuclear RNAs targeted for exosome-mediated degradation. It regulates cytoplasmic polyadenylation of metabolic mRNAs, including the glucose transporter SLC2A1/GLUT1, and mediates adenylation of miR-21 and H/ACA box snoRNAs, promoting their maturation or degradation depending on downstream processing 23. Recent evidence reveals TENT4B synthesizes unusually long "starRNA" molecules consisting of rRNA fragments with mixed tails, driving amyloidogenic phase transitions in nucleoli 4. Clinically, TENT4B inhibition selectively degrades hepatitis B virus RNA, suggesting therapeutic potential as an antiviral agent 5. Additionally, dysregulation of TENT4B-mediated miRNA adenylation contributes to hematopoietic failure in poikiloderma with neutropenia, with TENT4B inhibition rescuing defective hematopoiesis 6. TENT4B also stabilizes synthetic telomerase RNA therapeutics for extending replicative lifespan in stem cells 7.