Paralemmin3 is a recently identified protein that associates with the single immunoglobulin IL-1 receptor-related molecule (SIGIRR), a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Silencing of Paralemmin3 expression by RNAi inhibited the release of inflammatory cytokines in A549 cells after stimulation with lipopolysaccharide (LPS), suggesting Paralemmin3 may function as an adaptor in the LPS-TLR4 signaling pathway.