This review article explores the complex metabolic pathways of sphingolipids and their critical roles in various genetic and chronic diseases. Sphingolipids are bioactive lipids that serve multiple cellular functions, with ceramide (Cer) acting as a central hub in their metabolism. The review highlights the importance of sphingolipid metabolism in genetic diseases and disorders of the nervous and immune systems. It discusses the de novo synthesis pathway, which involves enzymes such as serine palmitoyltransferase (SPT), 3-ketosphinganine reductase, and ceramide synthase (CerS), and their regulation by various subunits and factors. The review also covers the catabolism of complex sphingolipids, including the hydrolysis of sphingomyelin and glycosphingolipids, and the role of enzymes such as glucosylceramidase and N-acetyl-hexosaminidase in their degradation. The article emphasizes the significance of sphingolipid metabolism in maintaining normal physiology and the consequences of its dysregulation in various diseases, including neurodegenerative disorders, metabolic diseases, and lysosomal storage diseases. The review also discusses the regulatory mechanisms of sphingolipid metabolism, including the influence of phosphorylation, post-translational modifications, and environmental factors such as oxidative stress and hypoxia. Overall, the review provides a comprehensive overview of the current understanding of sphingolipid metabolism and its implications in health and disease.This review article explores the complex metabolic pathways of sphingolipids and their critical roles in various genetic and chronic diseases. Sphingolipids are bioactive lipids that serve multiple cellular functions, with ceramide (Cer) acting as a central hub in their metabolism. The review highlights the importance of sphingolipid metabolism in genetic diseases and disorders of the nervous and immune systems. It discusses the de novo synthesis pathway, which involves enzymes such as serine palmitoyltransferase (SPT), 3-ketosphinganine reductase, and ceramide synthase (CerS), and their regulation by various subunits and factors. The review also covers the catabolism of complex sphingolipids, including the hydrolysis of sphingomyelin and glycosphingolipids, and the role of enzymes such as glucosylceramidase and N-acetyl-hexosaminidase in their degradation. The article emphasizes the significance of sphingolipid metabolism in maintaining normal physiology and the consequences of its dysregulation in various diseases, including neurodegenerative disorders, metabolic diseases, and lysosomal storage diseases. The review also discusses the regulatory mechanisms of sphingolipid metabolism, including the influence of phosphorylation, post-translational modifications, and environmental factors such as oxidative stress and hypoxia. Overall, the review provides a comprehensive overview of the current understanding of sphingolipid metabolism and its implications in health and disease.