In the present study, we employed both lipopolysaccharide-stimulated Jurkat T cells and cecal ligation and puncture (CLP)-induced sepsis models to demonstrate marked exacerbation of CD4+ T lymphocyte PANoptosis following NUFIP1 knockdown (KD), associated with impaired immune function, as evidenced by diminished cytokine production and T cell proliferation. The gene discussed is CD4; the disease is Sepsis.