Samd8, also known as SMSr (sphingomyelin synthase-related protein), is an endoplasmic reticulum (ER)-resident ceramide phosphoethanolamine (CPE) synthase [4,5,6,7,8]. It plays a crucial role in controlling ER ceramides, suppressing ceramide-induced apoptosis in cultured cells, and is involved in sphingolipid biosynthesis pathways [4,5,6,7,8]. Its N-terminal sterile α-motif (SAM) domain is important for its function and oligomerization [5,8].

In Smsr KO mice, SMSr/PE-PLC deficiency attenuated high-fat diet/fructose-induced fatty liver and NASH, as well as glucosylceramide accumulation-induced NASH, fibrosis, and tumor formation. This indicates that Samd8 may play a role in non-alcoholic fatty liver disease (NAFLD) development [3]. In addition, in the context of glioma, genes including Samd8 were identified as prognostic factors and used to construct a signature related to m5C RNA methylation modification, which is significant in predicting glioma patient survival [1]. In diabetic nephropathy, Samd8 was identified as a lipid metabolism-related key gene, and its high expression was confirmed in diabetic nephropathy samples, suggesting its potential role in this disease [2].

In conclusion, Samd8 is essential in regulating ceramide levels and apoptosis in cells. Model-based research, such as KO mouse models, has revealed its potential involvement in diseases like NAFLD, glioma, and diabetic nephropathy. These findings provide valuable insights into the biological functions of Samd8 and its significance in disease mechanisms, which may offer new directions for disease diagnosis and treatment.