Neu4, a mammalian sialidase, catalyzes the removal of sialic acid residues from glycoproteins, oligosaccharides, and sialylated glycolipids [2]. It has broad substrate specificity and is mainly located in the lysosome [2]. This enzyme is involved in multiple biological processes, such as the breakdown of sialylated glycoconjugates and the regulation of functionally important cellular events [1]. Genetic models, like gene knockout mice, have been crucial in studying Neu4's functions.

In Neu4 -/- mice, there is marked vacuolization and lysosomal storage in lung and spleen cells, along with an increased level of GD1a ganglioside and a decreased level of GM1 ganglioside in the brain [2]. These mice also exhibit neuroinflammation, manifested by elevated levels of GD1a and GT1b, increased LAMP1-positive lysosomal vesicles, Tunel-positive neurons, enhanced astrogliosis and microgliosis, and motor impairment, indicating Neu4's role in regulating ganglioside catabolism and inflammation in the mouse brain [2]. In hepatocellular carcinoma (HCC), NEU4 expression is significantly down-regulated, and overexpressing NEU4 inhibits cell motility by cleaving sialic acids on CD44, suggesting its potential as a regulator of HCC metastasis [3].

In summary, Neu4 plays essential roles in various biological processes, especially in the catabolism of gangliosides and regulation of cell motility. The study of Neu4 -/- mice has provided valuable insights into its functions in neuroinflammation and cancer-related processes, which may contribute to the development of new treatment strategies for related diseases.