CTTN (cortactin) is an actin-binding cytoskeletal protein that organizes the actin cytoskeleton and regulates cell morphology, migration, and focal adhesion dynamics 1. It facilitates lamellipodium formation and cell motility while stabilizing voltage-gated potassium channels at the plasma membrane through interactions with HDAC6 2. CTTN participates in receptor-mediated endocytosis via clathrin-coated pits and intracellular protein transport 3. In endothelial cells, CTTN regulates barrier function through S1P-mediated cytoskeletal rearrangement 4. Its expression is regulated by inflammatory factors (LPS, TNF-α) and mechanical stress via NF-κB, HIF, and NRF2 pathways in lung endothelial cells 5. Clinically, CTTN alterations associate strongly with cancer progression. Elevated CTTN correlates with lymph node involvement, advanced stage, and poor prognosis in head and neck squamous cell carcinoma 6. In melanoma, RNF128-mediated CTTN ubiquitination regulates EMT and stemness 7, while in gastric and esophageal cancers, CTTN phosphorylation by NEK9 and co-regulation with N-WASP drives metastatic cytoskeletal reorganization 89. CTTN serves as a biomarker in colorectal cancer liquid biopsies 10. In Alzheimer disease, ISG15-mediated CTTN acetylation impairs autophagosome-lysosome fusion, promoting tau accumulation 11.