Abstract Sepsis-induced acute lung injury (ALI) involves complex pathological mechanisms. 5-methylcytosine (m5C) RNA modification, catalyzed by methyltransferases like NOP2, plays a crucial role in regulating inflammation and cellular processes. However, the role of NOP2 and its potential regulation of m5C modification in sepsis-induced ALI remains unclear. An in vitro ALI model was established by treating human pulmonary epithelial A549 cells with lipopolysaccharide (LPS).