The major findings were that in patients with AF, Fn14 protein levels were increased in atrial myocytes and TWEAK expression was up‐regulated in PMBCs while TWEAK serum levels were decreased; in vitro, TWEAK increased Fn14 expression, and Fn14 siRNA knockdown counteracted the increased hypertrophy induced by TWEAK; activation of JAK2/STAT3 pathway was critical to the TWEAK‐induced hypertrophy in HL‐1 atrial myocytes. The gene discussed is TNFRSF12A; the disease is atrial fibrillation.