The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, a key defense system, and its target genes, including superoxide dismutase 1 (SOD1), heme oxygenase-1 (HO-1) and glutamate–cysteine ligase catalytic subunit (GCLc), are impaired in ECs exposed to high glucose (HG) levels (13) and in the retinas of donors with diabetic retinopathy (14). The gene discussed is KEAP1; the disease is diabetic retinopathy.