Toll-interacting protein (TOLLIP) is a ubiquitous intracellular adaptor protein involved in multiple intracellular signaling pathways. It plays a key role in mediating inflammatory intracellular responses, promoting autophagy, and enabling vacuole transport within the cell. TOLLIP is being increasingly recognized for its role in disease pathophysiology through involvement in these three primary pathways. Recent research also indicates that TOLLIP is involved in nuclear-cytoplasmic transfer, although this area requires further exploration. TOLLIP is involved in the pathophysiologic pathways associated with neurodegenerative diseases, pulmonary diseases, cardiovascular disease, inflammatory bowel disease, and malignancy. We postulate that TOLLIP plays an integral role in the disease pathophysiology of other conditions involved in vacuole trafficking and autophagy. We suggest that future research in this field should investigate the role of TOLLIP in the pathogenesis of these multiple conditions. This research has the potential to inform disease mechanisms and identify novel opportunities for therapeutic advances in multiple disease processes.
Keywords: Idiopathic pulmonary fibrosis; Inflammatory bowel disease; Neoplasms; Neurodegenerative diseases; TOLLIP.