CNOT6 is a catalytic deadenylase subunit of the CCR4-NOT complex that plays crucial roles in mRNA degradation and cellular homeostasis. As a 3'-5' exonuclease, CNOT6 degrades poly(A) tails of mRNAs, contributing to mRNA decay and gene expression regulation 12. The protein demonstrates diverse cellular functions beyond mRNA degradation, including prevention of cellular senescence and promotion of cell survival. CNOT6 knockdown leads to enhanced DNA mismatch repair through increased stability of MMR gene transcripts 2, while its depletion can promote senescence through p53-p21 and p16-pRB pathways 3. Disease relevance includes associations with multiple cancer types, where CNOT6 variants show causal relationships with cancer risk 4. Specifically, the rs2453176 polymorphism in CNOT6 is associated with increased lung cancer susceptibility 5. The protein also functions in metabolic regulation, as ENO1 recruits CNOT6 to degrade IRP1 mRNA, affecting iron homeostasis and ferroptosis in hepatocellular carcinoma 1. Additionally, CNOT6 expression is regulated by cap-adjacent m6Am modification, demonstrating its integration into broader RNA modification networks 6. These findings establish CNOT6 as a critical regulator linking mRNA metabolism to cellular fate decisions and disease pathogenesis.