CTTN (cortactin) is an actin-binding cytoskeletal protein that organizes the actin cytoskeleton and regulates cell shape, with particular importance in cell migration, focal adhesion dynamics, and endocytic processes. The protein promotes lamellipodia formation and controls neuronal morphology through interactions with binding partners including CTTNBP2. CTTN regulates endothelial barrier function by coordinating with ABL1 and MYLK in response to sphingosine 1-phosphate signaling, and stabilizes voltage-gated potassium channels at the cell membrane, including KCNH1 1. CTTN plays a central role in cancer progression by promoting cell invasiveness and metastasis formation across multiple tumor types. In colorectal cancer, CTTN is incorporated into extracellular vesicle-based biomarker panels (ColonTrack) that distinguish early-stage disease with >0.97 AUC 2. In head and neck squamous cell carcinoma, CTTN overexpression suppresses anoikis-dependent apoptosis, and CTTN knockdown impairs cytoskeletal formation and reduces anti-apoptotic capacity in patient-derived organoids 3. CTTN is implicated in hepatocellular carcinoma progression through interaction with hepatitis B virus X protein and activation of CREB1-mediated proliferation 4, and combined silencing of CTTN and FGF2 synergistically inhibits HCC cell migration and invasion via Ras/ERK pathway modulation 5. Recent evidence suggests CTTN acetylation by HDAC6 regulates autophagy-lysosome fusion in Alzheimer disease, with therapeutic implications for targeting ISG15-mediated pathways 6.