Neuraminidase 1, also known as N-acetyl-α-neuraminidase, is an enzyme found in lysosomes and encoded by the NEU1 gene. This enzyme is responsible for eliminating terminal sialic acids from glycoproteins and oligosaccharides. When mutations occur in the NEU1 gene, it leads to a particular lysosomal storage disorder known as sialidosis. Sialidosis is a rare genetic disorder that is inherited in an autosomal recessive manner. Sialidosis is classified into two subtypes: Type I, which has a later onset, and Type II, which presents with an early onset. In previous studies, an increase in glycolipid levels in visceral organs, and accumulation of sialyloligosaccharides and sialoglycoproteins were reported. However, the effect of NEU1 sialidase on secondary lipid expression levels in sialidosis pathology remains unknown. The relationship between lipid expression levels and inflammation of human and mouse sialidosis fibroblast cell lines was analyzed for the first time in this study. To understand the connection between secondary lipid alterations and inflammation in sialidosis molecular biological approaches and shotgun lipidome analysis were followed. The link between the secondary lipid alterations and their association with sialidosis was determined in our research. We have concluded that the findings not only provide the elucidation of the lipidome characteristics in sialidosis models of mice and patients, but they also have the potential to establish a connection between the lipidome and the occurrence of inflammation in sialidosis. Grasping the correlation between the changes in secondary lipids and inflammation may offer therapeutic strategies for sialidosis patients by modulating the expression of secondary lipids