Accumulating evidence suggests that moderate exercise confers significant benefits to patients with CKD.[9] Previous studies have demonstrated that irisin, secreted by skeletal muscles in response to physical exercise, plays a pivotal role in mediating the crosstalk between muscle and kidney, thereby attenuating renal damage in AKI and CKD.[45, 46] Despite the therapeutic potential of irisin in kidney damage, its clinical applications are hindered by inherent limitations such as a short half‐life, low membrane permeability, and limited organ‐specific targeting. Here, FNDC5 is linked to Nephropathy.