Volume-regulated anion channel subunit LRRC8B (LRRC8B)

Volume-regulated anion channel subunit LRRC8B (LRRC8B) is an integral membrane protein and one of the five members (A–E) of the LRRC8 family, which assemble into heteromeric complexes to form the volume-regulated anion channel (VRAC). VRACs mediate osmotically-activated Cl⁻ and organic osmolyte efflux and are essential for cell volume regulation, especially during swelling. LRRC8B is highly expressed in the brain and to a lesser degree in kidneys and lungs. While not able to form functional VRAC channels alone, LRRC8B combines with LRRC8A (and at least one other paralog) in the plasma membrane to yield a functional channel. Overexpression of LRRC8B has been shown to reduce ER-mediated Ca²⁺ release, with knockouts displaying altered ER Ca²⁺ store depletion. VRACs, including those with LRRC8B, are also implicated in processes such as apoptosis, angiogenesis, and neuroprotection/ injury. The protein possesses four transmembrane helices and a cytoplasmic C-terminal region rich in leucine-repeat motifs, contributing to channel structure and regulatory interactions[1][3][4]. Specific inhibitors or drugs targeting LRRC8B are not yet established, and functional heterogeneity among LRRC8A/B-E combinations remains an area of active research.

Other names

Leucine-rich repeat-containing protein 8BT-cell activation leucine repeat-rich proteinTA-LRRPKIAA0231Epididymis secretory sperm binding proteinLeucine rich repeat containing 8 family member B

Channel blockers of VRAC may inhibit apoptosis or angiogenesis by preventing osmolyte/anion efflux[1].