The exact cause of narcolepsy remains unknown. Nevertheless, evidence strongly suggests that genetic susceptibility plays a major role. Variations withing the immune-related genes such as HLA and T-cell receptor alpha predispose to narcolepsy but are not causal. Environmental factors are also strongly implicated but remain unknown. The best biological marker of narcolepsy with cataplexy is hypocretin deficiency (CSF hypocretin level < 110pg/ml). Hypocretin deficiency is most probably due to the disappearance of hypocretin-producing neurons in the brain. What causes hypocretin-deficiency remains to be established.