Focal segmental glomerulosclerosis (FSGS) is a histological picture of kidney damage caused by podocytopathy, that is, a pathological change in the podocytes that form the glomerular filtration barrier.[1] FSGS occurs in 20–30% of adults with nephrotic syndrome and up to 20% of dialysis patients.[2] It can be caused by genetic mutations in proteins such as nephrin or podocin, infections (eg, parvovirus, HIV), drugs (eg, calcineurin inhibitors, heroin), or hyperfiltration conditions (eg, obesity, hypertension, diabetic nephropathy).[1] Mutations in the TRPC6 gene, particularly gain-of-function types, lead to the familial form of FSGS by increasing the influx of calcium into podocytes, causing podocyte damage, disconnection, and proteinuria.[1][2] Inhibition of TRPC6 channels, for example with drugs such as BI 764198, SAR7334 or SH045, can reduce calcium influx and protect podocytes.[1][2] A phase 2 clinical trial with BI 764198 in patients with primary FSGS or TRPC6 mutations is underway, testing the reduction of proteinuria with daily dosing over 12 weeks.[2][4] NSAIDs such as diclofenac reduce the activity of both wild-type and mutated TRPC6 (eg, P112Q).[3] These findings suggest the potential of TRPC6 inhibition as a podocyte-targeted treatment for FSGS.[1][2]