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

## TL;DR

This review explores the role of chloride intracellular channels (CLICs) in lung diseases, highlighting their potential as new therapeutic targets.

## Contribution

The paper provides a comprehensive overview of CLICs' functional roles in lung pathophysiology, emphasizing underexplored therapeutic opportunities.

## Key findings

- CLICs exist in both membrane and soluble forms and are involved in chloride flux regulation and cellular processes.
- CLIC1, CLIC3, and CLIC4 are specifically linked to lung cancer, inflammation, and pulmonary hypertension.
- Distinct expression patterns of CLIC isoforms in lung cells suggest potential for targeted therapies.

## Abstract

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.