VPS9D1 encodes a guanyl-nucleotide exchange factor that localizes to the cytosol and endocytic vesicles, functioning in small GTPase regulation and protein binding. However, the retrieved literature predominantly addresses VPS9D1-AS1, an antisense long non-coding RNA transcribed from the VPS9D1 locus (chromosome 16.3), rather than the protein itself. VPS9D1-AS1 acts as a competitive endogenous RNA through multiple molecular mechanisms—functioning as a signal, scaffold, guide, and decoy regulator 1. It promotes cancer progression by sponging microRNAs (miR-377-3p, miR-520a-5p, hsa-miR-361-3p) and modulating signaling pathways including Wnt/β-catenin, TGF-β/ISG, and PI3K/AKT 2. In colorectal cancer, VPS9D1-AS1 upregulates VEGFA to promote angiogenesis 3, and a functional polymorphism (rs7206570) associates with advanced clinical stage 4. In endometrial and uterine corpus endometrial carcinoma, VPS9D1-AS1 enhances proliferation and epithelial-mesenchymal transition via the miR-377-3p/SGK1 and miR-520a-5p/BIRC5 axes 5, 6. In hepatocellular carcinoma, high VPS9D1-AS1 expression correlates with larger tumors, advanced TNM stage, and poor survival 7. Notably, gastric cancer shows decreased VPS9D1-AS1 expression associated with poor prognosis, suggesting cancer-context-dependent roles 8. Clinically, lipid-nanoparticle-delivered antisense oligonucleotides targeting VPS9D1-AS1 suppress colorectal cancer growth and enhance immune checkpoint blockade efficacy by activating MLKL-induced immunogenic cell death and increasing CD8+ T-cell infiltration 9, positioning VPS9D1-AS1 as both a diagnostic biomarker and therapeutic target.