Pattern recognition receptor (PRR) located on the cell surface that participates in the activation of innate immunity and inflammatory response (PubMed:11323673, PubMed:18490781). Recognizes small molecular motifs named pathogen-associated molecular pattern (PAMPs) expressed by pathogens and microbe-associated molecular patterns (MAMPs) usually expressed by resident microbiota (PubMed:29934223). Upon ligand binding such as bacterial flagellins, recruits intracellular adapter proteins MYD88 and TRIF leading to NF-kappa-B activation, cytokine secretion and induction of the inflammatory response (PubMed:20855887, PubMed:11489966). Plays thereby an important role in the relationship between the intestinal epithelium and enteric microbes and contributes to the gut microbiota composition throughout life (By similarity). Homodimer (PubMed:22173220). Interacts with MYD88 (via TIR domain) (PubMed:20855887). Interacts with TICAM1 (via TIR domain) (PubMed:20855887). Interacts with UNC93B1; this interaction is essential for proper TLR5 localization to the plasma membrane (PubMed:24778236). Highly expressed on the basolateral surface of intestinal epithelia (PubMed:11489966). Expressed also in other cells such as lung epithelial cells (PubMed:11489966, PubMed:18490781). Phosphorylated at Ser-805 by PKD/PRKD1; phosphorylation induces the production of inflammatory cytokines. Phosphorylated at Tyr-798 upon flagellin binding; required for signaling. Individuals with a common stop codon polymorphism in position 392 are unable to mediate flagellin signaling. This polymorphism acts in a dominant fashion and is associated with susceptibility to pneumonia caused by Legionella pneumophila [MIM:608556]. It also provides protection against systemic lupus erythematosus. A nonsense TLR5 polymorphism, resulting in p.Arg392Ter, confers resistance to melioidosis [MIM:615557], an infection caused by the Gram-negative, flagellated soil saprophyte Burkholderia pseudomallei. Carriers of this hypofunctional TLR5 variant may generate impaired inflammatory responses during melioidosis infection that result in reduced organ failure and lower mortality. Disease susceptibility is associated with variants affecting the gene represented in this entry. Belongs to the Toll-like receptor family.