TENT4A (terminal nucleotidyltransferase 4A) is a non-canonical poly(A) polymerase that catalyzes the transfer of ATP and GTP onto mRNA 3' poly(A) tails, creating heterogeneous mixed tails enriched with guanosine residues 1. This mixed tailing mechanism shields mRNAs from rapid deadenylation by the CCR4-NOT complex, thereby stabilizing mRNA and protecting it from active decay 1. TENT4A functions as a catalytic subunit within TRAMP-like complexes involved in post-transcriptional RNA quality control 2. Beyond mRNA regulation, TENT4A regulates DNA-damage tolerance by controlling translesion DNA synthesis through mRNA stability regulation of DNA polymerase η and the RAD18 E3 ligase, and indirectly via the CYLD tumor suppressor and long non-coding RNA PAXIP1-AS2 3. During oocyte-to-embryo transition, TENT4A incorporates internal guanosine residues into re-polyadenylated maternal mRNAs, essential for embryo cleavage 4. Clinically, TENT4A is required for hepatitis A and B virus replication; small molecule TENT4A inhibitors demonstrate potent antiviral activity in vitro and in vivo, with hepato-selective variants showing promise as therapeutic agents 25. Additionally, dysregulation of TENT4A-mediated miRNA adenylation contributes to hematopoietic failure in poikiloderma with neutropenia 6.