The combination of increased chemoreflex sensitivity, imbalanced preBötC excitation/inhibition activity, and reduced hypoglossal motoneuron excitability caused by disturbed HO-2 activity could all contribute to the increased loop gain that perpetuates transmission failures in respiratory motor output and disrupt upper airway patency in HO-2 null mice and OSA patients. The gene discussed is HMOX2; the disease is obstructive sleep apnea syndrome.