1.A.25.3.2
The LRRC8B homologue of 480 aas.  Its cytoplasmic domains are regulators of channel activity by allosteric mechanisms (Deneka et al. 2021).  LRRC8/VRAC chloride and anionic metabolite channels function in signaling and volume regulation (Thöne et al. 2025).  Besides conducting anions such as chloride, VRACs transport metabolites, neurotransmitters, immunomodulators, and drugs irrespective of their electrical charge. VRAC-mediated transport of these molecules has profound (patho)physiological significance. The recent identification of VRACs as heteromers of up to five different LRRC8 proteins allowed the roles of VRACs to be addressed with genetic and molecular tools. cryo-EM and mutagenesis yielded insights into the structure and function of VRACs (Thöne et al. 2025).