Chloride intracellular channel protein 4 (CLIC4)

Chloride intracellular channel protein 4 (CLIC4) is a member of the chloride intracellular channel family, structurally resembling omega-type glutathione-S-transferases and possessing both ion channel and enzymatic oxidoreductase activities[5]. CLIC4 is located predominantly intracellularly and is expressed in a wide range of tissues[1]. It functions in regulation of cellular chloride ion homeostasis, cell volume, and pH, and is critically involved in angiogenesis and endothelial tubulogenesis by facilitating the acidification and fusion of intracellular vacuoles in vascular endothelial cells[2][3]. CLIC4 also associates with cytoskeletal proteins (e.g., dynamin I, actin, tubulin) and may participate in cellular morphogenesis and signaling pathways such as those orchestrated by RhoA[1][5]. Dysregulated or altered expression of CLIC4 is implicated in disease contexts including cancer, vascular pathologies, and tissue responses to ischemic injury. Currently, no approved therapeutic drugs directly target CLIC4, but it remains under investigation as a potential therapeutic target and biomarker for angiogenesis-related diseases[2][3].

Other names

CLIC4p64H1HuH1DKFZP566G223CLIC4LH1huH1MTCLICchloride intracellular channel 4 likeintracellular chloride ion channel protein p64H1glutaredoxin-like oxidoreductase CLIC4epididymis secretory sperm binding protein

In preclinical research, inhibition of CLIC4 (e.g., by IAA-94) blocks its channel activity, affecting endothelial tubulogenesis and angiogenesis by impairing vacuolar acidification necessary for lumen formation[3].