TMOD3 (tropomodulin 3) is an actin-binding protein that caps the pointed end of actin filaments, regulating F-actin dynamics and cytoskeletal organization 1. Beyond its canonical role in preserving actin filament stability, TMOD3 participates in diverse cellular processes including lamellipodia remodeling during cell migration, adherens junction assembly, and exocytosis 1. TMOD3 expression is ubiquitous, with documented roles in developmental processes such as oocyte meiosis, erythropoiesis, and megakaryocyte morphogenesis 1. In the brain, TMOD3 contributes to neuronal plasticity through regulation of neurite outgrowth and dendritic spine formation 2. Clinically, TMOD3 dysregulation associates with multiple malignancies. In pancreatic adenocarcinoma, elevated TMOD3 correlates with poor prognosis and increased migration/invasion 3. In KRAS-mutant pancreatic cancer, TMOD3 promotes F-actin polymerization, facilitating autophagosome-lysosome fusion and ACSL4 degradation, thereby conferring ferroptosis and immunotherapy resistance 4. TMOD3 knockdown enhances CD8+ T cell infiltration and synergizes with PD-1 inhibition 4. In hepatocellular carcinoma, TMOD3 interacts with EGFR to activate PI3K-AKT signaling and increase MMP expression, promoting metastasis 5. TMOD3 also drives bladder cancer metastasis via YWHAG-mediated MAPK pathway activation 6. CDC6-TMOD3 interaction mediates paclitaxel resistance through focal adhesion assembly 7. Additionally, TMOD3 autoantibodies are detected in endometriosis 8.