Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition characterized by motor neuron loss. Environmental and occupational factors may contribute to disease onset and progression. Mounting evidence indicates that the peripheral immune system exacerbates disease by infiltrating the central nervous system (CNS) to directly damage motor neurons or by polarizing resident cells towards a destructive phenotype. We have shown that natural killer (NK) cells (cytotoxic and immune polarizing) may contribute to the shift in CNS immune polarity. Our objective is to identify unique gene expression signatures in circulating NK cells from sporadic and genetically linked ALS subjects (abnormal expansions in the C9ORF72 gene). We will correlate those changes with environmental exposures biomarkers using our tranSMART database. The data generated will determine a potential mechanism for environmental toxins in driving immune polarization and its role in RNA toxicity.