Two paradigms are the death of neuronal soma after direct activation of SARM1 by the neurotoxin vacor (Fig. 1) and the overexpression of SARM1 gain-of-function (GoF) variants, which are prevalent in amyotrophic lateral sclerosis (ALS) patients (see below) [18, 59]. The gene discussed is SARM1; the disease is amyotrophic lateral sclerosis.