GFUS (GDP-L-fucose synthase) encodes the terminal enzyme in the de novo biosynthesis pathway for GDP-L-fucose, catalyzing the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose through epimerase and reductase reactions 1. This enzyme is essential for protein fucosylation, a critical post-translational modification required for N- and O-glycan fucosylation 1. Biallelic variants in GFUS cause GFUS-CDG, a congenital disorder of glycosylation characterized by global developmental delay, mild coarse facial features, and faltering growth due to reduced GFUS protein levels and decreased GDP-L-fucose production leading to general hypofucosylation of glycoproteins in serum, leukocytes, thrombocytes, and fibroblasts 1. The disorder represents one of only five known CDG types related to impaired fucosylation 2. Clinically, GFUS-CDG can be effectively treated with oral L-fucose supplementation, which utilizes the GDP-L-fucose salvage pathway to normalize protein fucosylation within 4 weeks, resulting in moderate growth improvement and clear cognitive enhancement over 19 months of follow-up 1. Additionally, GFUS has been identified as part of prognostic gene signatures in both prostate cancer and triple-negative breast cancer, suggesting broader roles in oncology 34.