GMFG (glia maturation factor gamma) is an ADF/cofilin superfamily protein that primarily functions as a negative regulator of actin nucleation through Arp2/3 complex binding 1. At the molecular level, GMFG modulates cytoskeletal reorganization by controlling actin filament dynamics, which is essential for cellular processes including migration, adhesion, and integrin trafficking 2. GMFG regulates neutrophil chemotaxis by recruiting to the leading edge and modulating lamellipodia formation through p38 and PAK1/2 phosphorylation, and associates with WAVE2 to coordinate actin remodeling 3. The protein also facilitates β1-integrin recycling and prevents ubiquitin-mediated degradation, thereby supporting monocyte migration 2. Clinically, GMFG expression shows cancer-type-dependent significance. High GMFG expression predicts poor overall and disease-free survival in glioblastoma, lower grade glioma, lung squamous cell carcinoma, and ocular melanoma, but associates with improved outcomes in cutaneous melanoma and thymoma 1. GMFG promotes epithelial ovarian cancer and triple-negative breast cancer progression through epithelial-mesenchymal transition pathways 45. In chordoma, paracrine GMFG signaling from cancer-associated fibroblasts promotes tumor progression via ITGB1 targeting, correlating with poor patient survival 6. These findings suggest GMFG functions as a context-dependent oncogenic regulator with potential therapeutic targeting applications.