Armstrong et al studied disturbances in calcium homeostasis of skeletal muscle and suggested that they might play a key role in the development of exercise-induced muscle damage. Some of the immediate muscle changes after exercise have been attributed to protein degradation is initiated by non-lysosomal cysteine proteases, such as calpain. The elevation in intracellular calcium post-exercise can activate the calpains. Muscle tissue expresses three distinct calpains, including the well-characterized ubiquitous calpains - m- calpain, μ-calpain and n-calpain. Wang et al have concluded, in animal studies, that the increased levels of the protease m-calpain, promotes muscle injury whereas the calpastatin protein expression might execute a protective function for muscle injury. This has not yet been investigated in human studies. It can be hypothesised that the levels of calpastatin and m-calpain are important in explaining the variable response to exercise in IC and why some patients improve and others do not.