DMTN encodes dematin, a membrane-cytoskeleton-associated protein that functions as a key regulator of actin dynamics and cellular architecture. The protein directly binds F-actin and induces actin bundle formation, with activity regulated by phosphorylation via cAMP-dependent protein kinase A 1. DMTN interacts with β-spectrin through conserved SADH motifs, contributing to cortical cytoskeletal organization and membrane stability 1. Mechanistically, DMTN acts as a tumor suppressor by inhibiting RhoA-mediated signaling pathways and regulating cell cycle progression through downregulation of CDK1, CDK2, CDK4, and cyclin D1 2. The protein also modulates actin cytoskeletal rearrangements by binding to ARHGEF2 and inhibiting Rac1 signaling activation 3. DMTN expression is significantly reduced in multiple cancers, including glioblastoma and colorectal cancer, often due to promoter hypermethylation 23. This downregulation correlates with increased tumor invasion, metastasis, and poor patient survival 23. Additionally, DMTN deletions at chromosome 8.3 are associated with autism spectrum disorder, suggesting roles in neurodevelopment 4. The protein's dual function in cytoskeletal regulation and tumor suppression makes it clinically significant for cancer prognosis and potential therapeutic targeting.