In young mice, CCN5 knockdown induced a sarcopenia-like phenotype, encompassing skeletal muscle dysfunction and myosteatosis (fat mass: p < 0.01; intramyocellular triglyceride: 66.02 ± 3.798 vs. 104.5 ± 8.542 μg/mg tissue, p < 0.01). Here, CCN5 is linked to sarcopenia.