St3gal5, also known as lactosylceramide alpha-2,3-sialyltransferase and GM3 synthase, is crucial for the synthesis of gangliosides, a type of glycosphingolipid. Gangliosides play roles in various cellular processes, and their synthesis pathways are thus significantly influenced by St3gal5. Genetic models, such as knockout mouse models, have been instrumental in understanding its functions [4,7].

In mouse models, St3gal5-knockout (St3gal5-/ -) mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior, along with altered blood glucose levels, glucose tolerance, and EEG activity, suggesting its role in neuropsychiatric and metabolic functions [7]. Conditional deletion and overexpression of St3gal5 in smooth muscle cells in vivo showed that its down-regulation promoted ferroptosis of vascular smooth muscle cells in abdominal aortic aneurysm, indicating its importance in this disease [2]. In cancer research, down-regulation of St3gal5 promoted proliferation, migration, and invasion of bladder cancer cells in vivo and in vitro, and was associated with poor prognosis [3,8]. In clear cell renal cell carcinoma, its overexpression was positively correlated with tumor stage, grade, and poor prognosis, and was associated with CD8+ T cell exhaustion [5]. Also, exosomes from ST3GAL5high cancer cells promoted peritoneal dissemination by establishing a pre-metastatic microenvironment [6]. In lung cancer, ST3GAL5-synthesized a-series gangliosides inhibited TGF-β-induced epithelial-mesenchymal transition via TβRI degradation, and ST3GAL5 was weakly expressed in lung cancer tissues with good prognosis [1].

In conclusion, St3gal5 is essential for ganglioside synthesis and impacts multiple biological processes. Research using gene-knockout mouse models has revealed its significant roles in diseases like abdominal aortic aneurysm, various cancers, and potentially neuropsychiatric disorders. Understanding St3gal5 provides insights into disease mechanisms and potential therapeutic targets.