MYH9 encodes non-muscle myosin heavy chain IIA, a widely expressed cytoplasmic protein that generates intracellular chemomechanical force and regulates actin cytoskeleton translocation 1. Its functions are controlled through phosphorylation of light and heavy chains and protein interactions 1. MYH9 participates in diverse cellular processes including cytokinesis, cell migration, and angiogenesis 1. Beyond structural roles, phosphorylated MYH9 (particularly at Ser1943) functions as a signaling hub, recruiting proteins like USP22 to stabilize HIF-1α and regulate β-catenin/Wnt signaling through GSK-3β degradation 234. MYH9-related disease is an autosomal-dominant disorder characterized by macrothrombocytopenia, leukocyte inclusions, and variable renal failure, hearing loss, and cataracts 51. MYH9 variants also associate with non-syndromic deafness and chr22 kidney disease 1. Clinically, MYH9 dysregulation promotes cancer progression and therapeutic resistance across multiple malignancies. Elevated MYH9 expression correlates with lenvatinib resistance in hepatocellular carcinoma, platinum resistance in ovarian cancer, and cisplatin resistance in head and neck cancer, primarily through Wnt/β-catenin pathway activation 234. MYH9 also promotes liver fibrosis and gastric cancer progression through distinct signaling axes 67.