The five key differentially expressed ARGs (DE-ARGs) were screened through machine learning analysis, including ANKRD13C, PIK3R1, BSG, CEACAM6, and BRMS1; these DE-ARGs emerged as potential biomarkers for epilepsy and were involved in various signaling pathways and immune cell activities, and results were further experimentally validated. Here, PIK3R1 is linked to epilepsy.