Motoneurons that are vulnerable to degeneration in ALS (and mutant SOD1) pathology are the largest, fast fatigable motoneurons which lack Ca2+ buffering proteins (Lips and Keller, 1998, 1999; Palecek et al., 1999b; Pun et al., 2006; Hegedus et al., 2007), in fact they have Ca2+ buffering capacities that are 5 to 6 times lower than found in disease-resistant motoneurons (Lips and Keller, 1998; Palecek et al., 1999a). Here, SOD1 is linked to amyotrophic lateral sclerosis.