TLR4 interactor with leucine-rich repeats (TRIL)

TLR4 interactor with leucine-rich repeats (TRIL) is a type I transmembrane protein characterized by 13 leucine-rich repeats and a fibronectin domain, functioning primarily as an accessory component of the Toll-like receptor 4 (TLR4) signaling complex[2][6]. It is highly expressed in the brain and also found in tissues such as spinal cord, lung, kidney, and ovary[2]. TRIL mediates the cellular response to bacterial lipopolysaccharide (LPS), facilitating TLR4-dependent cytokine secretion and innate immune activation[1][2][6][7]. In neurons and glial cells, TRIL enhances the signaling of TLR3 as well as endosomal TLR4, promoting cytokine and interferon-stimulated gene expression following immune stimuli[1]. Its expression is rapidly induced by inflammatory stimuli, notably LPS, with particular relevance for neuroinflammation and hypothalamic responses to dietary fat[3][5]. Beyond immunity, TRIL has developmental roles, modulating Bmp and Nodal signaling by promoting Smad7 degradation and receptor ubiquitination, respectively[1]. Knockdown studies in mice demonstrate that loss of TRIL in the hypothalamus reduces inflammation, improves glucose tolerance, and protects from obesity in high-fat diet models, suggesting its potential as a therapeutic target in metabolic and inflammatory diseases[3][5]. No specific drugs targeting TRIL are currently known, and its modulation may carry safety implications due to its broad regulatory functions in immunity and metabolism.

Other names

TRILKIAA0644Leucine-rich repeat-containing protein KIAA0644TLR4 interactor with leucine-rich repeatsTLR4-interactor with leucine-rich repeats

Modulates Toll-like receptor 4 (TLR4) signaling in response to lipopolysaccharide (LPS). Enhances TLR3 signaling response. Accessory role facilitating cytokine and interferon induction via TLR pathways.