Our understanding of the role of SLCs in cell biology is not as advanced as that of other membrane proteins like channels and receptors. Some SLCs act as both transporters and receptors, called ‘transceptors,’ which help bring soluble proteins to membrane surfaces. While certain SLC proteins have been recognized as transceptors in mammalian cells, their working mechanisms are unclear. This gap in knowledge about SLC biology and cell signaling raises important questions. Why do some signaling pathways use SLCs as receptors instead of traditional receptors like G-protein coupled, ion-channel, or enzyme-linked receptors? Additionally, SLCs are found on internal membranes in mammalian cells, unlike GPCRs, which do not function solely in internal environments. All mammalian and fungal SLC-linked signaling systems operate within the endosome, lysosome, or Golgi, suggesting that SLCs possess unique biochemical properties to respond to changes in organelle balance that other systems do not have.

In 2019 we reported the structure and mechanism of the KDEL receptor, which is responsible for the retrieval of luminal chaperones from the Golgi back to the ER. Our discovery revealed how an SLC protein can function as a pH-driven signalling system, relaying information across the membrane as opposed to transporting nutrient and ions. Our work laid the foundation for further exploration of this concept in other systems in the cell.