Members of the CLIC family are largely soluble proteins that possess the intriguing property of spontaneous insertion into phospholipid bilayers to form integral membrane ion channels. Chloride intracellular channel 1 (CLIC1), a newly discovered member of the chloride channel protein family, has been implicated in multiple human cancers. CLIC1 is a Chloride Intracellular Ion Channel protein that exists either in a soluble state in the cytoplasm or as a membrane bound protein. CLIC1 acts as a putative oncogene in pancreatic cancer and may represent a novel diagnostic and therapeutic target for pancreatic cancer. Intracellular chloride channel protein 1 (CLIC1) participates in inflammatory processes by regulating macrophage phagosomal functions such as pH and proteolysis. CLIC1 is a novel therapeutic target to help reduce the adaptive immune response in autoimmune diseases. The expression of CLIC1 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of pancreatic ductal adenocarcinomas. Intracellular chloride channel 1 (CLIC1), a novel metamorphic protein, acts as a sensor of cell oxidation and is involved in inflammation.

Chloride intracellular channel protein 4, also known as Intracellular chloride ion channel protein p64H1 and CLIC4, is a member of the chloride channel CLIC family. It contains oneGST C-terminal domain. CLIC4 is a member of a family of intracellular chloride channels. It is regulated by p53, c-Myc, and tumor necrosis factor-alpha. CLIC4 is detected in epithelial cells from colon, esophagus and kidney (at protein level). CLIC4 has alternate cellular functions like a potential role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis. CLIC4 could promote endothelial cell proliferation and regulate endothelial morphogenesis (tubulogenesis). Expression of CLIC4 is prominent in heart, kidney, placenta and skeletal muscle. Overexpression of CLIC4 in cancer cells inhibits tumor growth. Conversely, overexpression of CLIC4 in tumor stromal cells stimulates tumor growth. Thus, CLIC4 participates in normal and pathological processes and may serve as a useful target for therapies in disturbances of homeostasis and neoplastic transformation. Loss of CLIC4 in tumor cells and gain in tumor stroma is common to many human cancers and marks malignant progression. Up-regulation of CLIC4 in tumor stroma is coincident with myofibroblast conversion, generally a poor prognostic indicator. Reactivation and restoration of CLIC4 in tumor cells or the converse in tumor stromal cells could provide a novel approach to inhibit tumor growth.