Background <p>In response to physical forces, skeletal muscles undergo a significant increase in protein anabolism. Piezo1 channels have emerged as key membrane mechanosensors in various tissues, including mammalian skeletal muscle. However, the potential role of Piezo1 channels in activating anabolic processes in muscle cells remains understudied. This study aimed to determine whether Yoda1, a specific Piezo1 activator, is able to promote protein anabolism in cultured skeletal muscle cells.</p> Methods and results <p>C2C12 myotubes were treated with Yoda1 (a specific activator of Piezo1), gadolinium (Gd³⁺) (a non-specific inhibitor of mechanically activated channels), or a combination of Yoda1 and Gd³⁺. After treatment, the myotubes were collected for Western blot or PCR analysis. Treatment with Yoda1 increased protein synthesis (PS) rates in parallel with enhanced AKT (Ser473), p70S6K (Thr389/Thr412), rpS6 (Ser 240/244) and GSK-3β (Ser9) phosphorylation. Incubation with Gd³⁺ alone did not induce significant changes in PS rates or intracellular anabolic markers. Treating myotubes with both Yoda1 and Gd³⁺ abolished the effects of Yoda1 on phosphorylation of p70S6K, rpS6 and PS rates.</p> Conclusion <p>Our findings show that Piezo1 activator Yoda1 is able to promote anabolic signaling and enhance PS rates in cultured mouse myotubes.</p>