Cers4, or ceramide synthase 4, is an enzyme in the sphingolipid pathway, catalyzing de novo ceramide synthesis [1]. Sphingolipid metabolism is closely related to various biological processes and disease states. Cers4 is involved in multiple pathways, and its function is crucial in maintaining normal physiological functions and may be related to disease development. Genetic models, such as knockout (KO) mice, are valuable for studying its role.

In a T-cell-specific CerS4 depletion model (CerS4 LCK/Cre), mice frequently suffered from pancolitis and developed more colon tumors, while CerS4 deficiency in epithelial cells (CerS4 Vil/Cre) led to smaller colon tumors [2]. In high-fat-diet-fed C57BL/6J mice, downregulation of CerS4 using shRNA-mediated hydrodynamic gene delivery reduced specific liver ceramides, promoted glycogen accumulation, enhanced insulin sensitivity, and mitigated hepatic insulin resistance [3].

In conclusion, Cers4 plays a significant role in inflammation, tumor development, and metabolic regulation. The use of KO and conditional knockout (CKO) mouse models has revealed its complex functions in colitis-associated cancer and hepatic insulin resistance, providing insights into potential therapeutic targets for related diseases.