Sphingolipid Metabolism in Oral Diseases: Pathogenic Mechanisms, Biomarkers, and Therapeutic Opportunities

Sphingolipids, essential structural components of biological membranes, form a framework that maintains their stability and fluidity. In addition to their structural function, these lipids and their metabolites participate in regulating multiple cellular processes, including proliferation, differentiation, gene expression, and apoptosis, thereby contributing to the maintenance of oral homeostasis. Dysregulation of sphingolipid metabolism is involved in the pathogenesis of several major oral diseases: oral squamous-cell carcinoma (OSCC), periodontitis, oral candidiasis, Sjögren’s syndrome (SS), and periapical diseases. Accordingly, a deeper understanding of sphingolipid biology may provide new opportunities for developing therapeutic strategies targeting these disorders. This review provides a comprehensive analysis of the structural characteristics and principal metabolic pathways of key sphingolipids (e.g., ceramide, sphingosine-1-phosphate [S1P], and glucosylceramide [GlcCer]), discusses their diverse roles in oral diseases, and summarizes recent advances in pharmacological approaches targeting enzymes involved in sphingolipid metabolism.