These in vivo and in vitro studies demonstrate that 1) CREBZF deficiency in macrophages improves insulin sensitivity via the crosstalk between ATM and adipocytes; 2) CREBZF promotes NF‐κB signaling by competitively inhibiting the binding of IκBα to p65; 3) Pharmacological inhibition of CREBZF corrects ATM activation and type 2 diabetes in mice; 4) CREBZF is highly expressed in ATM of obese humans and mice, which is correlated with proinflammation genes and insulin resistance in humans. The gene discussed is ATM; the disease is type 2 diabetes mellitus.