HMGB1, another RAGE interacting partner and a member of the family of damage associated molecular pattern molecules (Tang et al., 2011), has been implicated in the pathogenesis of a number of neurodegenerative disorders such as Parkinson’s disease (Gao et al., 2011), AD (Takata et al., 2004, 2012), multiple sclerosis and ALS (Lo Coco et al., 2007; Andersson et al., 2008; Casula et al., 2011; Mazarati et al., 2011) via inflammatory toll like receptor/RAGE signaling pathways activation. The gene discussed is AGER; the disease is multiple sclerosis.