This study demonstrated that FAP plays a decisive role in T2DM-associated HFpEF by activating the CaMKIIδ-Calcineurin A-NFATc2 signaling pathway, ultimately promoting myocardial hypertrophy, fibrosis, inflammation, oxidative stress, apoptosis, and energy metabolism dysfunction (Figure 8). Here, NFATC2 is linked to type 2 diabetes mellitus.