The vesicular nucleotide transporter (VNUT), also known as SLC17A9, is a member of the solute carrier superfamily, which contains ~300 proteins. Members of the SLC17 family are expressed in intracellular membranes and insulated vesicles such as the lysosomes¹.

SLC17A9 has 430 amino acids and predicted to have 12 transmembrane domains with both the carboxyl- and N-termini facing the same direction⁵. Although the human SLC17A9 ortholog displays sequence-specific modification of its N-terminus, SLC17A9 is highly conserved across species, which is believed to dictate its substrate preference⁵.

SLC17A9 is widely expressed in many tissues, especially in ATP containing vesicles⁴. In the brain, SLC17A9 is highly expressed in different regions such as the cortex, cerebellum, hippocampus, and olfactory bulbs, but also in astrocytes and microglia cells. SLC17A9 expression is also evident outside the central nervous system, such as in the gastrointestinal tract and the lungs⁴.

Unlike other SLC17 members, SLC17A9 is highly specific for phosphorylated nucleotides with particularly high affinity for ATP³. Silencing of SLC17A9 in PC12 cells revealed its fundamental role in ATP homeostasis as it dramatically reduced ATP concentrations in storage and secretory vesicles. In addition, SLC17A9 also plays a role in the immune system where it activates neutrophils by influencing ATP storage in secretory vesicles².

Under specific circumstances, SLC17A9 is involved in different pathological conditions. For example, in the spinal cord, SLC17A9 expression is associated with a general incline to feel pain³. Moreover, SLC17A9 is also involved in the development of glaucoma in mice, possibly by regulating ATP secretion³.