LRRC8D functions as a non-essential subunit of volume-regulated anion channels (VRACs), which are heteromeric complexes requiring LRRC8A plus at least one other family member (LRRC8B-E) for channel activity 1. These channels maintain cellular volume homeostasis in response to osmotic stress and conduct various anions, with channel properties depending on precise subunit composition 1. LRRC8D-containing VRACs exhibit unique substrate selectivity, with cryo-EM structures revealing that LRRC8D incorporation widens and increases hydrophobicity of the selectivity filter 2. The protein plays important roles in drug transport, as LRRC8A and LRRC8D are required for cisplatin and carboplatin uptake, with NAA60-mediated N-terminal acetylation facilitating this function 3. LRRC8D also mediates import of the antibiotic blasticidin-S 4. Notably, LRRC8D has opposing effects on immune signaling - while LRRC8A:C/E channels transport the immune messenger cGAMP, LRRC8D-containing channels inhibit cGAMP transport 5. In vascular smooth muscle cells, LRRC8D associates with NADPH oxidase 1 but shows high oxidant sensitivity compared to LRRC8C, suggesting different functional roles in inflammatory responses 6. These diverse functions highlight LRRC8D's importance in cellular homeostasis, drug sensitivity, and immune regulation.