SLC38A5/SNAT5 is a system N transporter that can mediate net inward or outward transmembrane fluxes of
neutral amino acids coupled with Na+ (symport) and H+ (antiport). Its preferential substrates are not only
amino acids with side chains containing
amide (
glutamine and
asparagine) or
imidazole (
histidine) groups, but also
serine,
glycine, and
alanine are transported by the carrier. Expressed in the pancreas, intestinal tract, brain, liver, bone marrow, and placenta, it is regulated at
mRNA and
protein levels by
mTORC1 and WNT/β-
catenin pathways, and it is sensitive to pH, nutritional stress,
inflammation, and
hypoxia. SNAT5 expression has been found to be altered in pathological conditions such as chronic inflammatory diseases, gestational complications, chronic
metabolic acidosis, and
malnutrition. Growing experimental evidence shows that SNAT5 is overexpressed in several types of
cancer cells. Moreover, recently published results indicate that SNAT5 expression in stromal cells can support the metabolic exchanges occurring in the tumor microenvironment of
asparagine-auxotroph
tumors. We review the functional role of the SNAT5 transporter in pathophysiology and propose that, due to its peculiar operational and regulatory features, SNAT5 may play important pro-
cancer roles when expressed either in neoplastic or in stromal cells of
glutamine-auxotroph
tumors.NEW & NOTEWORTHY The transporter SLC38A5/SNAT5 provides net influx or efflux of
glutamine,
asparagine, and
serine. These
amino acids are of particular metabolic relevance in several conditions. Changes in transporter expression or activity have been described in selected types of human
cancers, where SNAT5 can mediate
amino acid exchanges between
tumor and stromal cells, thus providing a potential therapeutic target. This is the first review that recapitulates the characteristics and roles of the transporter in physiology and pathology.