Physiopathological roles of vesicular nucleotide transporter (VNUT), an essential component for vesicular ATP release

Vesicular nucleotide transporter (VNUT) is the last identified member of the SLC17 organic anion transporter family, which plays a central role in vesicular storage in ATP-secreting cells. The discovery of VNUT demonstrated that, despite having been neglected for a long time, vesicular ATP release represents a major pathway for purinergic chemical transmission, which had been mainly attributed to ATP permeation channels. This article summarizes recent advances in our understanding of the mechanism of VNUT and its physiopathological roles as well as the development of inhibitors. Regulating the activity and/or the expression of VNUT represents a new and promising therapeutic strategy for the treatment of multiple diseases. • VNUT is the ninth member of the SLC17 organic anion transporter family. • VNUT is responsible for vesicular ATP release and plays an essential role in purinergic signaling. • VNUT is involved in various pathological processes such as inflammation pain perception and cancer. • Clodronate, the strongest VNUT inhibitor, acts as a vesicular ATP release blocker. • VNUT is a promising drug target to block purinergic signaling.