We investigate and report the biochemical consequence of this variant on SPT complex activity, which, similar to ALS-associated SPTLC1 variants, results in excess sphingolipid synthesis, in contradistinction to HSAN-associated SPTLC1 and SPTLC2 variants that result in SPT amino acid substrate shift and overproduction of 1-deoxySL. Here, AGXT is linked to amyotrophic lateral sclerosis.