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RefSeq (mRNA)



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Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene.[1][2][3]


It is an inhibitory adaptor protein within Toll-like receptors (TLR).[4] The TLR pathway is a part of the innate immune system that recognizes structurally conserved molecular patterns of microbial pathogens, leading to an inflammatory immune response.

Clinical significance

Polymorphisms in TLR genes have been implicated in various diseases like atopic dermatitis.[5] Recently, variations in the TOLLIP gene have been associated with tuberculosis and idiopathic pulmonary fibrosis.[6][7]


TOLLIP has been shown to interact with TOM1,[8] TLR 2,[9] TLR 4[9] and IL1RAP.[3]


  1. "Entrez Gene: TOLLIP toll interacting protein".
  2. Volpe F, Clatworthy J, Kaptein A, Maschera B, Griffin AM, Ray K (December 1997). "The IL1 receptor accessory protein is responsible for the recruitment of the interleukin-1 receptor associated kinase to the IL1/IL1 receptor I complex". FEBS Lett. 419 (1): 41–4. doi:10.1016/S0014-5793(97)01426-9. PMID 9426216.
  3. 3.0 3.1 Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, Lewis A, Ray K, Tschopp J, Volpe F (June 2000). "Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor". Nat. Cell Biol. 2 (6): 346–51. doi:10.1038/35014038. PMID 10854325.
  4. Bulut Y, Faure E, Thomas L, Equils O, Arditi M (July 2001). "Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling". J. Immunol. 167 (2): 987–94. doi:10.4049/jimmunol.167.2.987. PMID 11441107.
  5. Schimming TT, Parwez Q, Petrasch-Parwez E, Nothnagel M, Epplen JT, Hoffjan S (2007). "Association of toll-interacting protein gene polymorphisms with atopic dermatitis". BMC Dermatol. 7: 3. doi:10.1186/1471-5945-7-3. PMC 1832210. PMID 17362526.
  6. Shah JA, Vary JC, Chau TT, Bang ND, Yen NT, Farrar JJ, Dunstan SJ, Hawn TR (2012). "Human TOLLIP Regulates TLR2 and TLR4 Signaling and Its Polymorphisms Are Associated with Susceptibility to Tuberculosis". J Immunol. 189 (4): 1737–46. doi:10.4049/jimmunol.1103541. PMC 3428135. PMID 22778396.
  7. "Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study". The Lancet Respiratory Medicine. 1 (4): 309–317. doi:10.1016/S2213-2600(13)70045-6. PMC 3894577.
  8. Yamakami, Megumi; Yoshimori Tamotsu; Yokosawa Hideyoshi (Dec 2003). "Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin". J. Biol. Chem. United States. 278 (52): 52865–72. doi:10.1074/jbc.M306740200. ISSN 0021-9258. PMID 14563850.
  9. 9.0 9.1 Zhang, Guolong; Ghosh Sankar (Mar 2002). "Negative regulation of toll-like receptor-mediated signaling by Tollip". J. Biol. Chem. United States. 277 (9): 7059–65. doi:10.1074/jbc.M109537200. ISSN 0021-9258. PMID 11751856.

Further reading