FUCA2 (alpha-L-fucosidase 2) is a lysosomal hydrolase enzyme responsible for degrading fucosylated glycoconjugates by cleaving alpha-linked fucose residues from carbohydrate moieties 1. However, recent evidence suggests FUCA2 may have limited enzymatic activity under standard conditions, with FUCA1 serving as the primary fucosidase 1. FUCA2 is sorted to lysosomes via mannose 6-phosphate-dependent mechanisms 1. Clinically, FUCA2 functions as a pan-cancer oncogene with prognostic significance. It is upregulated across multiple tumor types and correlates with poor survival outcomes 2. In lung adenocarcinoma, FUCA2 promotes progression through the FUCA2/GGH axis, regulating cell cycle and epithelial-mesenchymal transition 3. In triple-negative breast cancer, cancer-associated adipocytes secrete FUCA2, which enhances tumorigenesis and metastasis via TM9SF3-dependent signaling 4. High FUCA2 expression correlates with increased tumor-associated macrophages, particularly M2-like macrophages, and immunosuppressive markers (PD-L1, TGFB1, IL10) 2. Beyond cancer, integrative multi-omics studies identified FUCA2 as a potential therapeutic target for sporadic Creutzfeldt-Jakob disease 5 and a biomarker in ankylosing spondylitis bone formation 6. FUCA2 also mediates Helicobacter pylori adhesion to gastric mucosa 7.