This study aimed to evaluate the transcriptomic differences between HS, PsO, and AD lesions, which drive these unique pathogenic features.<h4>Methods</h4>Bulk RNA sequencing was performed on 19 healthy controls (HC), 15 HS, 21 PsO, and 15 AD lesional skin samples.<h4>Results</h4>PsO lesions were defined by a strong interleukin (IL)-17 signature, and AD lesions had increased T helper (Th2) signaling. Here, IL17A is linked to Alzheimer disease.