Since the initial linkage of the P56S mutation in the human VAPB gene with motor neuron diseases, despite of the fact that patients carrying the P56S mutation presented with extremely heterogeneous clinical and pathological phenotypes, several murine models expressing P56S VAPB have been generated, aiming to recapitulate some clinical and pathological features of the patients and to examine the pathophysiological roles and underlying mechanisms of P56S VAPB. The gene discussed is VAPB; the disease is motor neuron disorder.