Human Toll Interacting Protein (TOLLIP) Protein

Background

TOLLIP is a negative regulator of Toll-like receptor (TLR) signaling, controlling inflammatory responses by inhibiting downstream activation of NF-κB and MAPK pathways. It functions as an adaptor protein that binds to TLRs and signaling intermediates, such as IRAK1 and TRAF6, to dampen excessive cytokine production and inflammatory responses during pathogen recognition. TOLLIP also plays a role in endosomal trafficking and autophagy, regulating receptor turnover and degradation to maintain immune homeostasis. It is widely expressed in immune cells, epithelial tissues, and organs like the liver and lungs, where it prevents chronic inflammation and excessive immune activation. Dysregulation or reduced expression of TOLLIP is associated with inflammatory diseases, autoimmune disorders, and increased susceptibility to infections. Knockdown studies reveal hyperactivated TLR signaling, elevated cytokine production, and impaired immune tolerance, highlighting its role as a key regulator of TLR signaling, inflammation, and immune homeostasis.