Slc2a3, also known as the gene encoding glucose transporter 3 (GLUT3), facilitates glucose diffusion across plasma membranes. It is crucial for ATP generation in the human brain, fueling essential biochemical processes like axonal transport and neurotransmitter release. Besides the central nervous system, GLUT3 is expressed in non-neural organs such as the heart and white blood cells, being involved in energy metabolism. In cancer cells, its overexpression contributes to the Warburg effect [1].

Placental SLC2A3 deficiency in sheep 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 [2]. In gastric cancer, SLC2A3 acts as a tumor promoter, accelerating aerobic glycolysis through a SLC2A3-STAT3-SLC2A3 feedback loop and promoting M2 subtype transition of macrophage infiltration [3]. In a Chinese Yunnan population, SLC2A3 (rs3931701) C > T variant increases the risk of congenital heart disease [4]. In oral squamous cell carcinoma, SLC2A3 promotes tumor progression via the lactic acid-promoted TGF-β signaling pathway [5]. In head and neck squamous cell carcinoma, SLC2A3 is a risk gene, associated with immune and tumor components in the tumor microenvironment, suppressing CD8+ T cells [6]. The SLC2A3 rs12842 polymorphism is inversely associated with the risk of Alzheimer's disease [7]. In head and neck squamous cell carcinoma, SLC2A3 may mediate disease progression via the NF-κB/EMT axis and immune responses [8]. In colorectal cancer, SLC2A3 may play a role in disease progression by regulating EMT and PD-L1 mediated immune responses [9]. MiR-103a can inhibit the proliferation of human colon cancer cells by targeting SLC2A3 [10].

In conclusion, Slc2a3 is essential for glucose transport and energy metabolism in various tissues. Its dysregulation is associated with multiple diseases, including fetal growth-related issues, cancer, and neurodegenerative diseases. Studies on Slc2a3, especially through in vivo models, help to understand its role in disease mechanisms, potentially providing novel therapeutic approaches.