FOXD2 is a forkhead box transcription factor located on chromosome 1 that functions as a DNA-binding transcription activator involved in embryogenesis and somatogenesis 1. As a class 1 FOX protein, FOXD2 contains a conserved forkhead domain and regulates transcription through RNA polymerase II-mediated mechanisms. The FOXD2 locus resides within a FOX gene cluster alongside FOXE3 1. Clinically, FOXD2 relevance primarily emerges through its adjacent long non-coding RNA, FOXD2-AS1, which is aberrantly upregulated across multiple malignancies including gastric, lung, bladder, colorectal, nasopharyngeal, esophageal, hepatocellular, thyroid, and skin cancers 2. High FOXD2-AS1 expression correlates with poor overall survival (HR=1.51) and disease-free survival (HR=1.66) 3, larger tumor size, and advanced TNM staging 4. FOXD2-AS1 promotes cancer progression through multiple mechanisms including P53 inhibition in glioma 5, TWIST1-mediated hepatocellular carcinoma progression 6, and miR-31/PAX9 axis regulation in retinoblastoma 7. Additionally, FOXD2-AS1 modulates oncogenic pathways including PI3K/AKT, Wnt/β-catenin, and NF-κB signaling, enhancing stemness and chemoresistance 8. FOXD2-AS1 represents a potential biomarker and therapeutic target in human cancers.