CNOT2 is an essential structural component of the CCR4-NOT complex, a major cellular mRNA deadenylase that regulates multiple aspects of gene expression 1. The protein is required for maintaining the structural integrity and deadenylase activity of the CCR4-NOT complex, as CNOT2 depletion destabilizes the complex and reduces its enzymatic activity 1. CNOT2 plays crucial roles in embryonic stem cell maintenance by repressing early trophectoderm transcription factors like Cdx2, helping maintain pluripotency in both mouse and human ESCs 2. The protein's deadenylase activity is dynamically regulated through MK2-mediated phosphorylation during osmotic stress, with phosphorylation reducing complex activity and affecting cellular stress resistance 3. CNOT2 is overexpressed in various cancers including breast, pancreatic, and liver cancers, where it promotes proliferation and angiogenesis through VEGF signaling pathways 456. Clinically, CNOT2 haploinsufficiency causes Intellectual Developmental disorder with Nasal speech, Dysmorphic Facies, and variable Skeletal anomalies (IDNADFS), characterized by developmental delay, hypotonia, learning difficulties, and distinctive facial features 78. Loss of CNOT2 function leads to P-body formation suppression and ER stress-induced apoptosis, highlighting its essential role in cellular viability 1.