Myoregulin

Where it comes from

Made in

Skeletal muscle, in every fibre type

Sent out by

Not secreted; a resident of the muscle fibre’s internal membranes

Acts on

• SERCA1 and SERCA2a (the pumps that return calcium after a contraction)

What it does

• Slows the return of calcium into the store, so relaxation is slower
• Mice without it run further and their muscles relax faster ¹
• The skeletal-muscle counterpart of the heart’s phospholamban

In medicine

• No medicine acts on it, no test measures it, and no human disease has yet been traced to a change in its gene, so it is on no gene panel
• It reaches the clinic only through the pump it holds back: a failing SERCA is part of heart failure, and losing the skeletal pump outright causes Brody disease, in which muscles relax too slowly

Beyond the body’s own use

• Turning its gene down is the therapeutic idea. Activating NR1D1, the clock protein that represses it, restored calcium handling and improved muscle structure and function in dystrophic mice, and muscle cells from boys with Duchenne dystrophy carry less of that protein ²
• The case for it as a target for exercise capacity rests on the treadmill of a knockout mouse; nothing has been tried in a person ¹
• What is being asked next is whether the two brakes on the skeletal pump, this one and sarcolipin, can be lifted separately, and what happens to a muscle that can no longer slow its own relaxation