Volume-regulated anion channel subunit LRRC8D (LRRC8D)

Volume-regulated anion channel subunit LRRC8D (LRRC8D) is a pore-forming component of the volume-regulated anion channel (VRAC), which controls cell volume by mediating the flux of chloride ions and diverse organic osmolytes in response to cell swelling[1][2][3][4]. LRRC8D must heteromerize with LRRC8A and other LRRC8 subunits (LRRC8B–E) to form functional VRACs, with the exact subunit composition conferring permeability to a broad spectrum of organic substrates—including amino acids and drugs like cisplatin[1][4]. Structural studies show LRRC8D-containing channels have a wider extracellular pore constriction compared to LRRC8A, suggesting a basis for their more permissive substrate selectivity[1][2][3]. LRRC8D is essential for the cellular entry of certain chemotherapeutics and antibiotics, making its expression a key factor in drug sensitivity, especially in tumors where downregulation of LRRC8D leads to chemoresistance[1].

Other names

Leucine-rich repeat-containing 8 VRAC subunit DLeucine-rich repeat-containing protein 8DLeucine-rich repeat-containing protein 5LRRC5HsLRRC8DFLJ10470UNQ213/PRO239Leucine rich repeat containing 8 family member D

Drug entry through VRAC when LRRC8D is present in heteromers (increases uptake of certain chemotherapeutic and antibiotic agents; loss reduces cellular uptake and leads to resistance)