Importantly, for ALS, p75NTR is expressed by motor neurons during development, only to be downregulated in adulthood and only re-expressed by motor neurons and Schwann cells following neuronal damage such as that in ALS animal models80,81 and in people with ALS.80,82,83 Additionally, p75NTR undergoes regulated intramembrane proteolysis, in which the 50 kDa ECD of the 75 kDa receptor is cleaved by TNF-α-converting enzyme, α-secretase/ADAM10/17.79,84 In the 1980s, DiStefano et al. 85 described the appearance of the ECD in rat urine via radioimmunoassay, post-bilateral sciatic nerve lesions. The gene discussed is ADAM10; the disease is amyotrophic lateral sclerosis.