HMGB2, a high‐mobility group domain protein, predominantly localizes in the nucleus and plays a vital role in cell proliferation and differentiation.[10, 11, 32] Previous studies have demonstrated that knockdown of HMGB2 impairs cardiac function and increases susceptibility to heart failure after transverse aortic constriction.[18] However, the biological function of HMGB2 in heart regeneration remains unexplored. Here, HMGB2 is linked to heart failure.