During his Ph.d-studies, Jakob Jensen Ulstrup has done research in the field of P4-ATPase lipid transporters. These transporters are exclusively found in eukaryotic organisms, where they are involved in lipid-based signaling ie. blood coagulation, apoptosis and biogenesis of vesicles. They are part of the P-type ATPase superfamily, which mainly consists of primary transport proteins that “pump” different cations across cellular membranes in a process driven by ATP. These pumps have been extensively studied over the last decades, both with respect to their biochemistry and structural composition. However, the flippases remain among the least understood members of the family, especially with regards to their transport mechanism, which allow them to transport a far larger substrate than a cation. This is one of the central questions asked in this field and is known as “the large substrate problem”. Jakob Jensen Ulstrup has studied the flippases Drs2 and Neo1 from the yeast organism Saccharomyces cerevisiae by employing such methods as macromolecular X-ray crystallography and single-particle electron microscopy. The main goal was to reach a better understanding of their transport mechanism and regulation. He has been part of achieving the first structural insight of a P4-ATPase and its auto-regulation.