Slc2a3, also known as the gene encoding glucose transporter 3 (GLUT3), is crucial for facilitating the diffusion of glucose across plasma membranes. It is mainly expressed in neurons, contributing to the brain's glucose supply for ATP generation, which is essential for axonal transport and neurotransmitter release. Besides the central nervous system, GLUT3 is also present in non-neural organs like the heart and white blood cells, participating in energy metabolism. It is also involved in the Warburg effect in cancer cells by meeting their increased glycolytic demands [1].

In sheep, placental Slc2a3 deficiency during the first-half of gestation leads to fetal hypoglycemia, reduced fetal development, and altered metabolic hormone concentrations, suggesting it may be the rate-limiting placental glucose transporter during this period [3]. In head and neck squamous cell carcinoma (HNSC), Slc2a3 is identified as a risk gene influencing the tumor microenvironment. Its up-regulation is associated with poor clinical outcomes, and it suppresses CD8+ T cells, potentially promoting tumor progression [2]. In gastric cancer, Slc2a3 acts as a tumor promoter, accelerating aerobic glycolysis and contributing to M2 subtype transition of macrophage infiltration [4]. In a Chinese Yunnan population, SLC2A3 (rs3931701) C > T variant increases the risk of congenital heart disease [5].

In conclusion, Slc2a3 is essential for glucose transport and energy metabolism in various tissues. Research on Slc2a3, especially through in vivo models like the sheep model with placental Slc2a3 deficiency, has revealed its significance in fetal development, as well as its roles in cancer and congenital heart disease, providing insights into potential disease mechanisms and therapeutic targets.