Nucleotide sugars are the activated form of monosaccharides that are used by glycosyltransferases during glycosylation. In eukaryotes the SLC35 family of solute carriers are responsible for their selective uptake from the cytoplasm into the lumen of the Endoplasmic Reticulum or Golgi apparatus. A recent crystal structure of the yeast GDP-mannose transporter, Vrg4, revealed a requirement for short chain lipids. Taken together with a marked difference in transport rate between the activated nucleotide sugar and nucleoside monophosphate, this suggested a complex network of regulatory elements control transport into these organelles. Here we report the crystal structure of the GMP bound complex of Vrg4, revealing the molecular basis for GMP recognition and transport. Molecular dynamics, combined with biochemical analysis reveal a lipid mediated dimer interface and mechanism for coordinating structural rearrangements during transport. Together these results provide further insight into how SLC35 family transporters function within the secretory pathway and shed new light onto the role that membrane lipids play in regulating transport across the membrane.