Trpc6 is a Ca(2+)-permeable non-selective cation channel. It belongs to the DAG-activated subfamily of channels and may also be involved in the store-operated calcium entry pathway [1,2]. It is expressed in various tissues such as the brain, smooth-muscle-containing tissues, kidney, immune and blood cells, and is crucial for many physiological processes [1].

Studies with Trpc6(-/-) mice suggest its role in regulating vascular and pulmonary smooth muscle contraction [1]. In the kidney, Trpc6 is an essential component of the slit diaphragm architecture of podocytes. Mutations and over-activation of Trpc6 lead to glomeruli injury. In diabetic kidney disease (DKD) models, factors like angiotensin II stimulate calcium influx through Trpc6, causing podocyte hypertrophy and foot process effacement, and ultimately albuminuria and renal injury [3]. Trpc6 knockout reduces glomerular manifestations of disease in some models and renal fibrosis caused by urinary tract obstruction, but is less effective at reducing DKD in mouse and rat models [4].

In conclusion, Trpc6 plays important physiological roles in smooth muscle contraction and kidney function, especially in maintaining the structure and function of podocytes. Gene knockout mouse models have revealed its significance in diseases like DKD and other renal disorders, providing insights into potential therapeutic targets for these diseases.