MARCKSL1 (MARCKS-like 1) is an actin-binding protein that regulates cell migration and cytoskeletal dynamics 1. It functions as a key regulator of F-actin organization and filopodium/lamellipodium formation, with phosphorylation status determining its effects on cell motility 1. When unphosphorylated, MARCKSL1 promotes cell migration; phosphorylation by MAPK8 stabilizes actin bundles and restricts movement 1. In cancer biology, MARCKSL1 plays a critical oncogenic role across multiple malignancies. In esophageal squamous cell carcinoma, MARCKSL1 interacts with F-actin and cortactin to promote invadopodia formation, enhancing cell invasion and ECM degradation; elevated MARCKSL1 correlates with lymph node metastasis and poor prognosis 2. In thyroid carcinoma, MARCKSL1 upregulation drives epithelial-mesenchymal transition and metastasis through the PI3K/Akt pathway 3. Circulating extracellular vesicle-derived MARCKSL1 serves as a potential non-invasive biomarker for metastatic colorectal cancer 4. In lung adenocarcinoma, the MARCKSL1 transcript variant 2 (lncRNA MARCKSL1-2) paradoxically suppresses docetaxel resistance by recruiting SUZ12 to silence HDAC1 and elevate miR-200b 5. MARCKSL1 also represents a component of senescent cancer-associated fibroblast signatures predicting hepatocellular carcinoma prognosis 6. These findings position MARCKSL1 as a multifunctional cancer regulator with therapeutic potential.