NALCN channel complex

Another key area of interest is the sodium leak channel NALCN. This ion channel is required for survival in mammals and gain- or loss-of-function mutations can result in devastating diseases in humans. We have recently shown that NALCN is only functional when it forms a complex with three other proteins, FAM155A, UNC79 and UNC80 (Chua et al, Science Advances, 2020). This breakthrough enabled the first detailed functional characterisation of NALCN and led our collaborators to obtain a structure of the entire NALCN channelsome, along with mechanistic and pharmacological insight (Kschonsak et al, Nature, 2020 and 2022). We continue to study the function and pharmacology, as well as disease-causing mutations of the NALCN channelsome.

Left: Close up view of ATP bound to a P2X receptor