We mapped our ALS associated SPTLC2 variant on the recently reported cryoelectron microscopy structure of the SPT-ssSPT-ORMDL complex.8 9 This in silico mapping shows that the SPTLC2 E260 residue, which is mutated in our patients, is distinct from the enzyme active site, where most HSAN1 SPTLC1 and SPTLC2 variants cluster. Here, AGXT is linked to amyotrophic lateral sclerosis.