FUCA1 encodes alpha-L-fucosidase 1, a lysosomal enzyme responsible for hydrolyzing alpha-1,6-linked fucose from the carbohydrate moieties of glycoproteins and glycolipids 1. The enzyme functions as a homotetrameric protein with aspartate-276 identified as the catalytic acid/base residue 2. FUCA1 is the exclusive lysosomal de-fucosylation enzyme, with FUCA2 showing no enzymatic activity despite prior speculation 1. Loss-of-function mutations in FUCA1 cause fucosidosis, a rare autosomal recessive lysosomal storage disorder characterized by accumulation of fucosylated glycoconjugates in lysosomes 3. Clinical manifestations include progressive neurological deterioration, dystonia, spasticity, coarse facies, visceromegaly, angiokeratoma, and recurrent infections 3. Novel mutations continue to be identified, including splice variants, frameshift deletions, and large deletions involving multiple genes 4, 5. Beyond lysosomal storage disease, FUCA1 functions as a p53 target gene with tumor-suppressive properties 6. FUCA1 expression is significantly decreased in colorectal cancers and correlates with disease progression 7. Enzymatic defucosylation by FUCA1 suppresses epidermal growth factor receptor activation and cancer cell growth 6. FUCA1 expression also associates with better osteosarcoma prognosis and enhanced immune microenvironment through macrophage activation 8.