Neuraminidase 4 (NEU4): new biological and physiological player

Abstract Sialidases are found in viruses, bacteria, fungi, avians, and mammals. Mammalian sialidases differ in their specificity, optimum pH, subcellular localization, and tissue expression. To date, four genes encoding mammalian sialidases (NEU1–4) have been cloned. This review examines the functional impact of NEU4 sialidase on complex physiological and cellular processes. The intracellular localization and trafficking of NEU4 and its potential target molecules are discussed along with its impact on cancer, lysosomal storage disease, and cellular differentiation. Modulation of NEU4 expression may be essential not only for the breakdown of sialylated glycoconjugates, but also in the activation or inactivation of functionally important cellular events.