Our results demonstrated that FKBP12.6 protects heart from AngII‐induced cardiac hypertrophy through preventing the activations of the Ca2+/calmodulin‐dependent signalling pathways such as calcineurin/NFATc4, CaMKII/MEF‐2, AKT/GSK3β/NFATc4 and AKT/mTOR pathways. The gene discussed is AKT1; the disease is cardiac hypertrophy.