By combining computational approaches with independent dataset validation, our results offer novel insights into the molecular mechanisms of α-HB in sepsis, specifically demonstrating that: (1) α-HB exposure may significantly impact disease progression through immune/inflammatory pathway modulation, as evidenced by our unsupervised clustering revealing two distinct sepsis subtypes with differential survival outcomes; (2) Molecular docking confirms α-HB’s potential interactions with key targets (APEX1, CTSD, SLC40A1, PIK3CB), providing mechanistic explanations for its biological effects. The gene discussed is CTSD; the disease is Sepsis.