MNAT1 (menage à trois 1) is a core component of the CDK-activating kinase (CAK) complex located on chromosome 14 1. As an assembly factor, MNAT1 stabilizes the cyclin H-CDK7 complex to activate cell cycle CDKs (CDK1, CDK2, CDK4, CDK6) through threonine phosphorylation and participates in RNA polymerase II transcription initiation via TFIIH integration 1. Beyond canonical cell cycle regulation, MNAT1 exhibits oncogenic functions in multiple malignancies. In colorectal cancer, MNAT1 is overexpressed and directly binds p53, facilitating its ubiquitin-mediated degradation through MDM2 interaction, thereby promoting cell proliferation and suppressing apoptosis 2. In head and neck squamous cell carcinoma, CCNE2 upregulates MNAT1 to drive cisplatin resistance, invasion, and migration 3. Similarly, in osteosarcoma and oral squamous cell carcinoma, MNAT1 overexpression promotes malignant progression and cell proliferation 45. Conversely, MNAT1 reduction contributes to disease pathogenesis in non-malignant contexts. Decreased MNAT1 expression promotes endothelial necroptosis and blood-brain barrier dysfunction in Alzheimer's disease through A20 and LRP1β degradation, worsening amyloid-β accumulation 6. Similarly, NAT1/NAT2 deficiency impairs spermidine-mediated acetylhypusination of RIPK1, increasing inflammation and type 2 diabetes susceptibility 7.