We found that perhexiline maleate (Pex), which is a prophylactic antianginal drug widely used for stable angina but its use markedly declined in the early 1980s after reports of hepatotoxicity and peripheral neuropathy, suppressed the Id1 promoter activity and mRNA expression of native Id1 and alkaline phosphatase by down-regulating phosphorylation of Smad1/5/8. This evidence concerns the gene ID1 and peripheral neuropathy.