DHPS (deoxyhypusine synthase) catalyzes the NAD-dependent transfer of a butylamine moiety from spermidine to a critical lysine residue of eIF5A precursor protein, forming the intermediate deoxyhypusine 1. This post-translational modification, termed hypusination, is essential for eIF5A maturation and function 2. DHPS operates through a well-defined enzymatic mechanism with a specific substrate binding pocket 2. Mechanistically, DHPS-mediated hypusination regulates diverse cellular processes. In intestinal epithelial cells, hypusinated eIF5A enhances translation of aldehyde detoxification enzymes, protecting against infectious colitis and colorectal cancer development 34. In melanoma, DHPS-mediated hypusination promotes proliferation by regulating m6A modification through METTL3 and facilitates vasculogenic mimicry via FGFR2 and c-KIT expression 56. In ovarian cancer, DHPS elevation correlates with poor survival and promotes epithelial-to-mesenchymal transition via the TGFβ pathway 7. DHPS dysregulation associates with multiple diseases. Patients with ulcerative colitis and Crohn's disease exhibit reduced DHPS expression and hypusinated eIF5A levels 3. The DHPS/eIF5A pathway plays essential roles in various cancers, immune-related diseases, glucose metabolism disorders, neurological diseases, and aging 2. DHPS inhibitors represent promising therapeutic targets for cancer treatment and potentially other disease indications 256.