SUMF1 encodes formylglycine-generating enzyme (FGE), a critical oxidase that catalyzes the post-translational conversion of cysteine residues to 3-oxoalanine (formylglycine) in target proteins 12. This modification is essential for activating arylsulfatases and alkaline phosphatases, which use the hydrated 3-oxoalanine form as a catalytic nucleophile 12. Known SUMF1 substrates include GALNS, ARSA, STS, and ARSE 12. SUMF1 functions primarily in the endoplasmic reticulum lumen, where it performs oxidoreductase activity on nascent sulfatases 3. Its localization is controlled through sequential interactions with protein disulfide isomerase, ERGIC-53, and ERp44, which regulate ER retention, activation, and secretion 3. SUMF1 mutations cause multiple sulfatase deficiency (MSD), a rare autosomal-recessive lysosomal storage disorder affecting multi-organ systems 45. Beyond MSD, emerging evidence suggests SUMF1 dysregulation associates with disease severity in COVID-19 through inflammatory pathways 6, cystic fibrosis via the CFTR-linc-SUMF1-2 axis 7, and glioma progression through effects on cell proliferation and immune microenvironment 8. SUMF1 was also identified as a novel biomarker for early Parkinson's disease 9.