Motor Neuron Disease or Amyotrophic lateral sclerosis(ALS) is a rapidly progressive, fatal neurodegenerative disorder of unknown etiology. It exists in both mendelian-inherited and sporadic forms. In the Irish population, we have shown multiple haplotype associations with the gene ANG in SALS independent of observed mutations in the gene (1). Our observations, coupled with the identification of series of susceptibility genes in different populations, has supported the notion that SALS is a complex genetic disease, in which genetic background and environmental risks interact leading to the process of neurodegeneration (2,3). Although originally considered as a pure motor degeneration, there is now considerable clinical, neuropathological and genetic overlap between ALS and other neurodegenerative diseases, particularly frontotemporal dementia (FTD) (4,5). Despite recent advances, common pathways shared between ALS and other neurodegenerative disease remain to be fully elucidated at clinical, molecular and genetic level. This will be best achieved by careful phenotype analysis in characterized populations, by identifying common susceptibility genes, and by identifyng new pathways in neurodegeneration and neuroprotection that can be then targeted for therapeutic intervention.