Chloride voltage-gated channel 3 (CLC-3) (CLC-3)

Chloride voltage-gated channel 3 (CLC-3) is a member of the CLC family of chloride channels and transporters, primarily functioning as a late endosomal/lysosomal 2Cl-/1H+ antiporter (UniProt: P51790). It plays a critical role in maintaining the acidic environment of intracellular organelles, which is essential for protein degradation and vesicular trafficking (NCBI Gene: 1182). Beyond its role in acidification, CLC-3 is involved in cell volume regulation and the regulation of cell proliferation and apoptosis. In the context of disease, CLC-3 is highly overexpressed in certain cancers, particularly malignant gliomas, where it facilitates cell migration and invasion by modulating cell volume changes (PMID: 12110604). It is also implicated in cardiovascular diseases like hypertension and various neurodegenerative conditions. While specific, high-affinity drugs targeting CLC-3 are still in development, it has been identified as a target for compounds like chlorotoxin and certain non-specific chloride channel blockers (PubMed: 24561151). The channel's involvement in insulin secretion and neurotransmitter loading into synaptic vesicles further highlights its physiological importance (PMID: 11514513). Therapeutic strategies often focus on inhibiting its activity to reduce tumor invasiveness or manage vascular remodeling.

Other names

CLCN3Chloride channel protein 3ClC-3H+/Cl- exchange transporter 3

Inhibition of chloride ion transport or H+/Cl- exchange to disrupt cellular pH homeostasis and volume control.