Pathophysiology of ALSALS can be divided into two major groups, sporadic ALS (sALS) and familial ALS (fALS) (Figure 2.1.2-1). [11][12][13] These two cases cannot be distinguished by molecular genetic techniques since their clinical picture is very similar. The exact cause for ALS is not known as of today, but it is generally accepted that genetic and environmental factors play a huge role in the course of the disease, no matter whether sALS or fALS is present. [7] It is worth noting that genetic factors are much better understood than environmental factors, the consequence being that fALS can be described much more precisely than sALS.Environmental factors that are being discussed controversially are smoking, exposure to air pollution, head injury, physical activity and sports as well as chronical exposure to certain substances such as lead, other heavy metals, or pesticides. [14] The list is not exhaustive, though specific personal characteristics might be as relevant as the known environmental factors. In case of fALS, the autosomal dominant pathway of inheritance mainly consists of mutations in the following genes: tardbp (5%), c9orf72(40%), vapb (3%), fus (5%), and sod1 (20%). A large contribution is attributed to unknown gene factors that could not be identified yet. [13] The sporadic form of ALS is significantly less explored in terms of genetic factors. Only 11% of all cases can be attributed to known genes, the majority of them are also linked to fALS. The vast majority of sALS-affected genes are unknown and their investigation will provide much needed knowledge towards potential treatment of ALS. [13,15] Figure 2.1.2-1. Etiology of ALS and the most common genetic factors for fALS (A) and sALS (B). [13]