FES is a protooncogene that encodes a protein-tyrosine kinase distinct from c-Src, c-Abl and other nonreceptor tyrosine kinases. FES was originally identified as the cellular homolog of several transforming retroviral oncoproteins. FES plays a role in regulating cytoskeletal rearrangements and inside out signalling that accompany receptor ligand, cell matrix and cell-cell interaction. Genetic analysis using transgenic mouse model implicate FES in the regulation of inflammation and innate immunity. FES modulates the innate immune response of macrophages to LPS challenge, in part, by regulating the internalization and down-regulation of the TLR4 receptor complex.