Intracellular Chloride Channels: A Rising Target in Lung Disease Research.

Chloride intracellular ion channels (CLICs) represent a relatively underexplored class of chloride channels and are included in a research initiative that focuses on druggable genes that have not been well studied yet. As a unique family, CLICs exist in membrane and soluble forms and play a role in regulating chloride flux and modulating various aspects of cellular biology. To date, six mammalian CLICs have been cloned and characterized at molecular and physiological levels. The respiratory system, responsible for gas exchange between the atmosphere and the human body, has recently been shown to express CLICs with functional relevance in lung pathophysiology, including lung carcinoma, inflammation, and endothelial dysfunction. Notably, the expression patterns of CLIC isoforms in lung cell types are distinct. Among them, CLIC1, CLIC3, and CLIC4 have been investigated more extensively, particularly in the context of lung cancer, inflammatory diseases, and pulmonary arterial hypertension. A deeper understanding of the role of CLICs in regulating lung cellular function may pave the way for developing novel therapeutic strategies to treat pulmonary disorders. In this review, we summarize the expression and functional roles of CLICs in lung pathophysiology, with particular emphasis on CLIC1, CLIC3, and CLIC4.