TOLLIP (Toll Interacting Protein) functions as a critical regulatory adapter protein that connects innate immunity signaling with autophagy pathways. In immune signaling, TOLLIP acts as a negative regulator by inhibiting Toll-like receptor and IL-1 receptor pathways, though specific mechanistic details are not provided in the available literature 1. Most significantly, TOLLIP serves as a selective autophagy receptor that mediates the autophagic degradation of ubiquitinated proteins and cellular structures 234. TOLLIP facilitates the clearance of diverse cellular components including metabolic proteins like MCT1, transmembrane proteins like TMEM63A, and pathological aggregates such as poly-glycine proteins 234. The protein plays essential roles in maintaining cellular homeostasis by promoting autophagosome formation and autophagic flux 4. TOLLIP also participates in mitophagy, where it can be exploited by pathogens like influenza virus to degrade antiviral signaling proteins 5. Additionally, TOLLIP contributes to stress granule disassembly mechanisms in cellular stress responses 6. Clinical relevance includes potential therapeutic targeting in diseases where TOLLIP-mediated autophagy is disrupted, such as neurodegenerative disorders involving protein aggregates and cancer progression 43.