Lrrc8a, also known as Swell 1, is a core component of volume-regulated anion channels (VRACs). These channels play a crucial role in maintaining cellular stability by regulating cell volume, which is essential for various cellular processes such as cell survival, growth, and proliferation. LRRC8A is involved in multiple signaling pathways, including those related to cell adhesion, MAPK, AMPK, and chemokine signaling, and is associated with inflammation and immune cell activation [1].

In conditional knockout mouse models: Conditional knockout of Lrrc8a in microglia/macrophage (M/Mφ) accelerates hematoma clearance, reduces neuronal death, and improves functional recovery after intracerebral hemorrhagic stroke by promoting M/Mφ phagocytosis via the AMPK-Nrf2-CD36 pathway [2]. In myofibroblasts, specific knockout of Lrrc8a greatly attenuates myofibroblast transformation, fibrotic remodeling, and ventricular dysfunction after myocardial infarction, as LRRC8A participates in TGF-β1-induced myofibroblast transformation via activating JAK2-STAT3 signaling [3].

In conclusion, Lrrc8a is vital for regulating cell volume and is involved in multiple biological processes. Gene knockout models, especially in specific cell types, have revealed its role in diseases such as intracerebral hemorrhagic stroke and myocardial infarction-related fibrosis. Understanding Lrrc8a's functions provides potential therapeutic targets for these and other related diseases [2,3].