ELMO3 (engulfment and cell motility 3) is a critical regulator of cytoskeletal dynamics and cell migration. Functionally, ELMO3 forms a tight complex with DOCK1-5 guanine nucleotide exchange factors to regulate RAC1 spatiotemporal activation and signaling 1. The protein acts as an upstream regulator of RAC GTP-binding during cell migration and is essential for F-actin polymerization 2. ELMO3 expression is transcriptionally regulated by the intestine-specific transcription factors CDX2 and SP1 2. Clinically, ELMO3 has emerged as a significant biomarker in multiple malignancies. Elevated ELMO3 expression is associated with poor prognosis in non-small cell lung cancer (AUC=0.917, 92.8% sensitivity) 3, gastric cancer 4, colorectal cancer 5, head and neck squamous cell carcinoma 6, and laryngeal cancer 7. ELMO3 knockdown inhibits cancer cell proliferation, invasion, migration, and metastasis across multiple tumor types, suggesting its role in tumor progression 45. In neurodevelopmental disorders, biallelic ELMO3 mutations impair RAC1-GTP loading and cause autism spectrum disorder with developmental delay 1. ELMO3 thus represents both a diagnostic/prognostic cancer biomarker and a neurodevelopmental disease gene.