NEU2 (neuraminidase 2) is a cytosolic exo-alpha-sialidase that catalyzes hydrolytic cleavage of terminal sialic acid residues from glycoconjugates 1. The enzyme cleaves sialic acids from glycoproteins, glycolipids, and oligosaccharides, displaying substrate specificity based on sialyl linkage positions and supramolecular organization 2. NEU2 preferentially hydrolyzes alpha-(2→3)-sialylated gangliosides (GD1a, GT1B) over alpha-(2→8)-sialylated forms, cleaves monomeric GM1 ganglioside, and processes milk oligosaccharides like alpha-(2→3)-sialyllactose, but shows no activity toward colominic acid or miscellar GM1 2. The enzyme is exclusively expressed in skeletal muscle tissues 3 and localizes to the cytosol 1, with optimal activity at pH 5.6 1. In cells, NEU2 can physically interact with cytosolic β-glycosidase GBA3, enabling coordinated degradation of sialylated free N-glycans through mutual stabilization 4. As a member of the mammalian neuraminidase family 5, NEU2 participates in catabolism of glycolipids and glycoproteins, though specific disease associations remain incompletely characterized. Selective inhibitors like siastatin B and synthetic sialyldendrimers have been developed to modulate NEU2 activity 67.