MCF2 is a guanine nucleotide exchange factor (GEF) that activates Rho family GTPases, particularly RAC1 and CDC42, through catalysis of GDP-to-GTP exchange 1. The gene contains tandem Dbl-homology and pleckstrin-homology domains characteristic of the Dbl GEF family 1. MCF2 localizes to the plasma membrane and cytoplasm, where it regulates actin-dependent cytoskeletal processes and cell migration 2. Functionally, MCF2 plays critical roles in macrophage efferocytosis, where putrescine-mediated HuR stabilization of Dbl mRNA enhances RAC1-driven actin reorganization for apoptotic cell internalization 2. During corticogenesis, MCF2 controls embryonic migration of cortical projection neurons, and pathogenic mutations impair cortical laminar positioning, causing congenital bilateral perisylvian syndrome (CBPS) 3. Clinically, MCF2 variants have been identified in rare neurological diseases 4. DNA methylation of MCF2 correlates with psychotherapy response in borderline personality disorder patients 5. MCF2 hypermethylation occurs in esophageal atresia promoters within dysregulated Rho GTPase signaling pathways 6. As an X-linked gene, MCF2 demonstrates sex-specific associations with Alzheimer's disease neuropathology and cognitive decline, particularly in females 7.