Our latest endeavours into protein engineering show that ASICs are exquisitely sensitive to side chain length and charge at a conserved Lys in the extracellular domain – one carbon can make all the difference! Big thanks to postdocs former postdocs Debayan Sarkar and Iacopo Galleano for leading this effort, assisted by former MSc students Sofie Ou and Gül Uzun, as well as the contributions by lab alumnus Keith Khoo and Gerbrand J.v.d.H. van Noort from Leiden (Netherlands)! We are very grateful for funding by the Lundbeck Foundation and the DFF. The current version of the manuscript can be found HERE.