SLC1A5

SLC1A5 is a human gene that encodes the protein ASCT2, also known as the alanine/serine/cysteine transporter 2. It is a member of the solute carrier family SLC1 and functions as a plasma membrane transporter that mediates sodium-dependent transport of neutral amino acids. ASCT2 primarily acts as an exchange (antiporter) transporter, shuttling intracellular and extracellular neutral amino acids in a sodium-dependent manner rather than driving net uptake on its own.

ASCT2 is widely expressed in multiple tissues, with notable presence in the kidney and intestinal epithelium, where it contributes to the cellular uptake and homeostasis of neutral amino acids. The protein is also found in various other tissues and is upregulated in certain physiological and pathological conditions.

Structurally, ASCT2 belongs to the SLC1 family of transporters, and functional transport occurs as part of a trimeric complex in the membrane. Each protomer participates in substrate binding and translocation through conformational changes that couple amino acid exchange to the sodium gradient.

Substrate specificity for ASCT2 includes several neutral amino acids, with a particular emphasis on glutamine, which plays a central role in cellular metabolism. Other substrates can include serine, alanine, asparagine, and related amino acids, reflecting the transporter’s broad specificity for small neutral residues.

Clinical and research significance has grown around SLC1A5 because of its role in cellular glutamine uptake and metabolic reprogramming in rapidly proliferating cells, including cancer cells. Overexpression of SLC1A5 has been observed in diverse cancers and is being explored as a therapeutic target. Experimental inhibitors and substrate analogs, such as GPNA, have been used to study ASCT2 function and assess potential anti-cancer strategies.