NEU1 encodes neuraminidase 1, a lysosomal sialidase that catalyzes the removal of terminal sialic acid residues from glycoproteins and glycolipids 1. NEU1 requires association with protective protein/cathepsin A (CTSA) to form a functional lysosomal multienzyme complex and be transported to lysosomes, where it becomes active at acidic pH 2. Beyond its classical lysosomal catabolic functions, NEU1 exhibits broader cellular roles, including cell surface activities where it modulates receptor structure and function 1. Recent studies reveal NEU1's involvement in pathological processes, such as cardiac hypertrophy where it translocates to the nucleus and interacts with GATA4 to promote fetal gene expression 3. NEU1 also mediates growth factor-triggered endocytosis through pH-dependent sialic acid removal, enabling galectin-driven internalization of glycoproteins like integrins 4. Clinically, NEU1 mutations cause sialidosis, an autosomal recessive lysosomal storage disorder characterized by sialylglycan accumulation and ranging from mild cherry red spot-myoclonus syndrome to severe infantile forms with coarse features and developmental delay 5. Over 90 pathogenic NEU1 variants have been identified, predominantly missense mutations showing significant phenotypic diversity 6. Therapeutic targeting of NEU1 shows promise for cardiovascular diseases, aging-related conditions, and genetic epilepsies 378.