DPYSL3 (dihydropyrimidinase-like 3) functions as a metastasis suppressor gene with dual roles in neuronal development and cancer progression. In normal physiology, DPYSL3 is necessary for class 3 semaphorin signaling and subsequent cytoskeletal remodeling, playing crucial roles in axon guidance and neuronal growth cone collapse 1. The protein participates in pyrimidine nucleobase catabolic processes through its dihydropyrimidinase activity. In cancer contexts, DPYSL3 acts as a tumor suppressor, with reduced expression promoting metastatic behavior across multiple cancer types. In prostate cancer, DPYSL3 downregulation correlates with increased cell motility and metastasis 23. Similarly, DPYSL3 knockdown in lung cancer enhances cell migration, invasion, and TGF-β-induced epithelial-mesenchymal transition 4. The gene's tumor suppressor function is regulated by promoter hypermethylation in hepatocellular carcinoma, where reduced expression correlates with poor prognosis and extrahepatic recurrence 5. Conversely, in some contexts like urothelial carcinoma, DPYSL3 overexpression is associated with aggressive behavior and poor outcomes 6. DPYSL3 expression is also altered in neurological conditions including epilepsy 1 and serves as a prognostic biomarker in various cancers 7.