In Gak-KO mice podocytes, we found increased NF-κB p65 activity and a striking increase in IκBα cleavage; these phenotypes were summarily abrogated by loss of podocyte-associated Capns1. Given these findings, we posit that the improvement of glomerulosclerosis and kidney function observed following podocyte-specific deletion of Capns1 is partially associated with the restoration of IκBα, which in turn inhibits the overactivated NF-κB p65/GADD45B pathway. The gene discussed is NFKBIA; the disease is glomerulosclerosis.