P4-ATPases: how an old dog learnt new tricks - structure and mechanism of lipid flippases.

•P4-ATPase drive the transport of phospholipids directed to the cytoplasmic leaflet.•Structures for yeast and human P4-ATPases have been determined by cryo-electron microscopy.•P4-ATPases are autoregulated by direct interactions between the C-terminus and ATPase domains, which also gates lipid access.•Future work must address the structural determinants of substrate specificity and release.