MYO9B encodes an unconventional myosin that functions as an actin-based motor protein with dual enzymatic activities: ATPase and GTPase activator functions 1. The protein binds actin with high affinity and acts as a GTPase activator for RHOA, regulating cell migration through RhoA signaling 2. Its GTPase activity is calcium-inhibited and can be modulated by interaction with the ROBO1 receptor, which impairs RHOA binding and increases active GTP-bound RhoA levels 2. In disease contexts, MYO9B variants associate with multiple conditions. A CRISPR-validated enhancer variant in MYO9B mediates coronary artery disease (CAD) risk by regulating vascular cell motility 3. MYO9B polymorphisms show associations with inflammatory bowel disease susceptibility in Caucasian populations, with rs1545620 showing protective effects while rs962917 and rs1457092 increase risk 4. The MYO9B R133Q polymorphism associates with increased type 1 diabetes risk and enhanced dendritic cell function 5. In cancer, MYO9B cooperates with MIRO2 to promote invasion and metastasis through suppression of RhoA activity 6. These findings underscore MYO9B's critical role in vascular cell biology, immune regulation, and cancer progression.