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cern.Volumetric muscle loss (VML) impacts skeletal muscles and causes damage to associated tissues such as blood vessels and other structural tissues. Despite progress in the VML field, current preclinical approaches are often ineffective at restoring muscle volume. Additional research is paramount to develop strategies that improve muscle mass and function, while restoring supporting tissues. We highlight mechanisms that govern normal muscle function that are also key players for VML, including intracellular calcium signaling/homeostasi