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Fsp27 plays a crucial role in muscle performance.

Fsp27 was previously identified as a lipid droplet-associated protein in adipocytes. Various studies have shown that it plays a role in the regulation of lipid homeostasis in adipose tissue and liver. However, its function in muscle, which also accumulate and metabolize fat, remains completely unknown. Our present study identifies a novel role of Fsp27 in muscle performance. Here we demonstrate that Fsp27-/- and Fsp27+/- mice, both males and females, had severely impaired muscle endurance and exercise capacity compared to wild-type controls. Liver and muscle glycogen stores were similar amongst all groups fed or fasted, and before or after exercise. Reduced muscle performance in Fsp27-/- and Fsp27+/- mice was associated with severely decreased fat content in the muscle. Furthermore, results in heterozygous Fsp27+/- mice indicate that Fsp27 haploinsufficiency undermines muscle performance in both males and females. In sum, our physiological findings reveal that Fsp27 plays a critical role in muscular fat storage, muscle endurance, and muscle strength.