This video examines Escherichia coli (E. coli), a common gram-negative bacterium responsible for nosocomial infections affecting over 100 million patients worldwide each year. It explains that bacterial lipopolysaccharide (LPS) from E. coli binds to toll-like receptor 4 (TLR4) and its co-receptors—cluster of differentiation protein 14 (CD14) and myeloid differentiation factor 2 (MD2)—collectively known as the LPS receptor complex. This video highlights that LPCAT2 participates in lipid-raft assembly through phospholipid remodeling. Previous research has shown that LPCAT2 co-localizes in lipid rafts with TLR4 and regulates macrophage inflammatory response. However, no published evidence has existed on how LPCAT2 influences the gene expression of the LPS receptor complex induced by smooth or rough bacterial serotypes. This video uses RAW264.7—a commonly used experimental murine macrophage model—to study the effects of LPCAT2 on the LPS receptor complex by transiently silencing the LPCAT2 gene, infecting the macrophages with either smooth or rough LPS, and quantifying gene expression. It demonstrates that LPCAT2 only significantly affected the gene expression of the LPS receptor complex in macrophages infected with smooth LPS. This video provides novel evidence that the influence of LPCAT2 on macrophage inflammatory response to bacterial infection depends on the LPS serotype, and it supports previous evidence that LPCAT2 regulates inflammatory response by modulating protein translocation to lipid rafts.