Sodium-coupled neutral amino acid transporter 5 (SLC38A5)

Sodium-coupled neutral amino acid transporter 5 (SLC38A5) is a member of the solute carrier family 38 that facilitates bidirectional, sodium-dependent movement of neutral amino acids—particularly glutamine, asparagine, histidine, serine, glycine, methionine, and alanine—across cell membranes via a coupled Na⁺ symport and H⁺ antiport mechanism. This transporter is regulated by nutrient status and key signaling networks including mTORC1 and Wnt/β-catenin, with expression sensitive to changes in pH, inflammation, and hypoxia. SLC38A5 is implicated in key metabolic pathways such as glutaminolysis and one-carbon metabolism, affecting cell proliferation, nutrient acquisition (via macropinocytosis), and intracellular pH homeostasis. It is upregulated in cancers (including triple-negative breast cancer and pancreatic ductal adenocarcinoma), chronic inflammatory states, gestational complications, and certain neurodevelopmental and retinal vascular diseases. It is primarily expressed in secretory and absorptive tissues including brain, pancreas, intestine, liver, bone marrow, and placenta. Amilorides can inhibit SLC38A5 activity, and functional loss impairs diverse cellular functions and may have therapeutic relevance for cancer.

Other names

SNAT5System N transporter 2 (SN2)JM24PP7194solute carrier family 38 member 5transport system Nsystem N transporter 2sodium-coupled neutral amino acid transporter 5

Inhibition of amino acid transport and macropinocytosis (by amilorides); Modulation of mTORC1, glycolysis, mitochondrial respiration (in response to substrate transport inhibition)