Lrrc8a, also known as Swell 1, is a core component of volume-regulated anion channels (VRACs) [5]. VRACs are activated by hypotonic conditions and play a crucial role in the regulatory volume decrease process. This gene is involved in maintaining cellular stability, regulating immune cell activation, and is associated with multiple biological processes and disease-related pathways [2]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its functions.

In T cells, deletion of Lrrc8a impairs T cell activation and function, especially under weak TCR stimulation, indicating that Lrrc8a-controlled cell volume regulation is required for optimal T cell activation [1].

In allergic rhinitis, knocking down Lrrc8a in a mouse model reduces eosinophil infiltration, down-regulates the expression of NADPH oxidase-related factors and Th2 inflammatory markers, and decreases NF-κB pathway activation, suggesting Lrrc8a may be a potential target for treatment [2].

In intracerebral hemorrhagic stroke mouse models, conditional knockout of Lrrc8a in microglia/macrophage accelerates hematoma clearance, reduces neuronal death, and improves functional recovery by promoting phagocytosis through the AMPK-Nrf2-CD36 pathway [3].

In myocardial infarction mouse models, myofibroblast-specific knockout of Lrrc8a attenuates myofibroblast transformation, fibrotic remodeling, and ventricular dysfunction, revealing its role in cardiac fibrosis regulation [4].

In conclusion, Lrrc8a is essential for regulating cell volume, immune cell function, and inflammation. KO/CKO mouse models have demonstrated its significance in diseases such as T cell-related immune responses, allergic rhinitis, intracerebral hemorrhagic stroke, and myocardial infarction-induced cardiac fibrosis. These findings highlight Lrrc8a as a potential therapeutic target in these disease areas.