Solute carrier family 1 member 5 (SLC1A5) (SLC1A5)

Solute carrier family 1 member 5 (SLC1A5), also known as ASCT2, is a sodium-dependent neutral amino acid transporter that primarily mediates the uptake of glutamine, a conditionally essential nutrient for rapidly proliferating cells [5, 14]. In many cancers, SLC1A5 is significantly upregulated to support "glutamine addiction," where it fuels the tricarboxylic acid (TCA) cycle and activates the mTORC1 pathway to drive tumor growth and survival [9, 15]. Beyond its role in tumor cells, SLC1A5 is critical for the metabolic reprogramming and activation of Natural Killer (NK) cells and T cells, particularly following cytokine stimulation with IL-2 or IL-15 [4, 8]. While pharmacological inhibition of SLC1A5 with small molecules like V-9302 is a promising strategy to starve tumor cells and induce apoptosis or ferroptosis, it presents a therapeutic challenge because it may simultaneously impair the anti-tumor activity of immune cells within the tumor microenvironment [15, 16]. Consequently, SLC1A5 represents a complex target where the benefits of metabolic starvation of the tumor must be balanced against the potential for unintended immunosuppression [4, 20].

Other names

Alanine-serine-cysteine transporter 2ASCT2ATB(0)Neutral amino acid transporter ASCT2M7V1RDRCAAAT

Competitive inhibition of sodium-dependent neutral amino acid transport, primarily blocking glutamine uptake to suppress glutaminolysis and mTORC1 signaling.