Abstract: Dynamics and mechanics of expression of disease biology are symptomatic of an aberrant homeostatic mechanism affecting primarily the corticospinal tract within the scope of developmental biology of motor neuron diseases. It is significant that full development of plasticity mechanics and loss of such plasticity is the cause of loss of trophic maintenance of the skeletal myofiber as component systems of the integral motor unit. The neuromuscular junction as a site of plasticity in its own right would complement the integrative functionality and homeostatic mechanics of involvement of a whole broad range of lesions in motor neuron diseases that contrasts with the universal and relatively simple clinical expression of myofiber atrophy. It would further appear that consequences of motor system biology of disease are symptomatic of genetic consequences in terms beyond simple mechanics of trophic deprivation. A toxic gain of functionality of lesions consists of cardinal features of a progressiveness of involvement as exemplified by mutations in Copper/Zinc superoxide dismutase in some familial forms of amyotrophic lateral sclerosis.