Volume-regulated anion channel subunit LRRC8C (LRRC8C)

The **volume-regulated anion channel subunit LRRC8C** (LRRC8C) is a transmembrane protein that forms part of the VRAC complex, a hexameric ion channel responsible for mediating chloride and other anion currents across cell membranes in response to cell swelling[1][2][3]. VRAC complexes are heteromers comprising various combinations of LRRC8A-E subunits, with LRRC8A being obligatory for function and LRRC8C modulating channel properties and activation[2][3]. LRRC8C, by interacting with the core LRRC8A subunits, destabilizes their tightly closed conformation, facilitating activation of the VRAC under osmotic stress[1][2]. LRRC8C is highly expressed in the heart among other tissues[3]. Pathogenic variants in LRRC8C can drive aberrant channel activity, which is linked to abnormal cell volume regulation – an underlying factor in diseases such as cancer progression and brain ischemia[1]. To date, there are no highly selective pharmacological agents targeting LRRC8C individually, and research continues into its specific roles in human health and disease[3].

Other names

Factor for adipocyte differentiation 158FAD158AD158TimesLeucine-rich repeat-containing protein 8CLeucine rich repeat containing 8 family member Chypothetical protein AD158

Channel modulators (such as DCPIB) inhibit VRAC activity, altering cell volume regulation and potentially downstream processes like cell survival