ENAH (Enabled Homolog) is an actin-associated protein and member of the Ena/VASP family that functions as a highly efficient actin elongation factor 1. Primary function: ENAH regulates cytoskeleton remodeling through F-actin polymerization, promoting cell migration, filopodial dynamics, and axon guidance 2. The human gene spans approximately 157 kb with 14 exons and produces a major 4.8 kb transcript with alternatively spliced isoforms 2. Mechanism: ENAH operates through multiple molecular pathways. Its EVH1 and EVH2 domains mediate interactions with binding partners including BECN1 and profilin, while the PRD domain facilitates actin polymerization-dependent processes 1. ENAH contributes to autophagosome formation and trafficking through actin-dependent mechanisms 1. At the nuclear envelope, ENAH regulates nesprin-2 to control nuclear architecture and gene expression 3. Disease relevance: ENAH is significantly upregulated in oral squamous cell carcinoma (OSCC) and esophageal squamous cell carcinoma (ESCC), correlating with poor patient survival 45. In OSCC, PI3K/AKT/β-catenin signaling upregulates ENAH to promote migration and growth via ITGB5/Src axis 4. ENAH-202 lncRNA regulates the ZNF502/VIM axis in OSCC progression 6. In lung cancer, TRIM67 interaction with ENAH inhibits apoptosis and autophagy 7. Clinical significance: ENAH represents a therapeutic target for cancer treatment, with potential strategies including miR-375-mediated ENAH suppression 5.