TRPC6 encodes a calcium-permeable non-selective cation channel that forms receptor-activated channels in various tissues including brain, smooth muscle, kidney, and immune cells 1. The channel exhibits a characteristic doubly rectifying current-voltage relationship and is six times more permeable to calcium than sodium 1. TRPC6 is directly activated by the second messenger diacylglycerol (DAG) and regulated by tyrosine or serine phosphorylation, with extracellular calcium having inhibitory effects while intracellular calcium/calmodulin provides potentiating effects 1. Structurally, the channel contains both inhibitory and activating calcium-binding sites that couple intracellular calcium concentrations to basal channel activity 2. TRPC6 plays critical roles in kidney function as an essential component of the podocyte slit diaphragm architecture 1. Gain-of-function mutations in TRPC6 cause familial focal segmental glomerulosclerosis (FSGS) by allosterically abolishing the inhibitory effects of intracellular calcium 2 3. In diabetic kidney disease, TRPC6 mediates calpain activation, which impairs podocyte autophagy and accelerates kidney injury 4. The channel is also implicated in cardiovascular regulation, with genetic variants associated with daytime napping behavior and cardiometabolic outcomes 5. TRPC6 represents a promising therapeutic target for kidney diseases, with structure-based drug design efforts underway 2 6.