MKNK1 is a serine/threonine kinase that regulates translation initiation by phosphorylating eIF4E, the 5' mRNA cap-binding protein, thereby controlling mRNA translation efficiency 1. As a downstream target of MAPK signaling pathways (ERK and p38), MKNK1 integrates stress responses and growth signals to modulate protein synthesis 1. Mechanistically, MKNK1 participates in the MNK/eIF4E axis that controls translation of specific mRNAs, including c-MYC in KRAS-mutant cancers 2. Beyond translation, MKNK1 regulates acinar cell secretion and proliferation in pancreatic tissue and influences nociceptor excitability in sensory ganglia 3, 1. Clinically, MKNK1 dysregulation contributes to multiple diseases. In aging-associated pancreatitis, miR-503-322 from senescent β-cells targets MKNK1 in acinar cells, impairing secretion and promoting autodigestion 3. MKNK1 overexpression mediates trastuzumab resistance in HER2-positive breast cancers through YB-1 activation and RSK-dependent phosphorylation 4. In KRAS-mutant colorectal cancer, MNK/eIF4E inhibition sensitizes tumors to mTORC1 inhibition by suppressing c-MYC expression, with implications for patient stratification 2. Additionally, MKNK1 regulates cancer stem cell properties and metabolic adaptation in breast and pancreatic cancers 5, while miR-370-3p-mediated MKNK1 inhibition suppresses adipogenesis and lipid accumulation 6. These findings establish MKNK1 as a therapeutic target across multiple cancer types and metabolic disorders.