Peroxisome proliferator-activated receptor alpha (PPARα), a key nuclear transcription factor that regulates keratinocyte differentiation and epidermal lipid metabolism, is markedly downregulated in AD (Kuai et al., 2024), leading to impaired barrier integrity and defective lipid synthesis, which further supported by PPARα agonist-induced barrier restoration in ex vivo skin model (Majewski et al., 2021). Here, PPARA is linked to Alzheimer disease.