TIAM1 is a guanine nucleotide exchange factor (GEF) that activates RAC1, CDC42, and to a lesser extent RHOA, serving as a molecular switch linking extracellular signals to cytoskeletal rearrangement 1. The protein regulates diverse cellular processes including cell migration, adhesion, cytoskeletal dynamics, and membrane trafficking 2. TIAM1 functions through both canonical GEF activity and non-canonical protein interactions; for example, it forms a nuclear complex with TRIM28 to silence protocadherins and promote epithelial-to-mesenchymal transition in lung cancer 3. In pancreatic β-cells, TIAM1-mediated RAC1 activation supports physiological insulin secretion but paradoxically contributes to dysfunction under metabolic stress 4. TIAM1 has prominent roles in cancer pathogenesis. NSD2-catalyzed methylation of TIAM1 at K724 enhances RAC1 signaling and promotes colon cancer metastasis 5. TIAM1 overexpression in neuroblastoma correlates with adverse prognosis, and TIAM1 knockdown suppresses proliferation, invasion, and promotes apoptosis 6. In cardiovascular disease, SNO-Septin2-mediated TIAM1-RAC1 axis activation drives macrophage-dependent inflammation and extracellular matrix degradation in aortic aneurysm and dissection 7. A recent multi-ancestry GWAS identified TIAM1 as a novel Alzheimer's disease-associated locus 8, though the mechanistic relationship remains to be elucidated.