Short transient receptor potential channel 6 (TRPC6)

Short transient receptor potential channel 6 (TRPC6) is a non-selective cation channel that mediates the influx of calcium and sodium ions into the cytoplasm in response to various stimuli, including phospholipase C-coupled receptor activation and mechanical stretch [1, 2]. It is widely expressed in tissues such as the kidney, lungs, and vasculature, where it regulates essential processes like podocyte stability and smooth muscle tone [3, 4]. Gain-of-function mutations or over-expression of TRPC6 are major drivers of focal segmental glomerulosclerosis (FSGS) and other proteinuric kidney diseases due to calcium-induced podocyte injury [5, 6]. Additionally, TRPC6 is implicated in pulmonary arterial hypertension and certain cancers, where it promotes cell proliferation and remodeling [7, 8]. Current drug development efforts focus on small-molecule inhibitors to mitigate excessive calcium influx and protect against tissue damage in renal and cardiovascular pathologies [9, 10].

Other names

Transient receptor potential cation channel subfamily C member 6TRP-6TRPC-6Focal segmental glomerulosclerosis 2FSGS2

TRPC6 inhibitors (antagonists) block the non-selective cation channel, preventing the pathological influx of calcium and sodium ions into cells, which reduces downstream signaling pathways like calcineurin/NFAT that contribute to podocyte damage and vascular remodeling.