Due to the key role PDI appears to play in ALS, a genome association study examined the effects of two specific single-nucleotide polymorphisms (SNPs) in the P4HB gene, which codes for PDI, which showed a significant association with familial ALS, suggesting that P4HB is a modifier gene in ALS susceptibility and may present a potential therapeutic target (Kwok et al., 2013). Here, P4HB is linked to amyotrophic lateral sclerosis.