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The immune response plays a pivotal role in the pathogenesis of diseases. Toll-like receptor 4 (TLR4), as an intrinsic immune receptor, exhibits widespread in vivo expression and its dysregulation significantly contributes to the onset of various diseases, encompassing cardiovascular disorders, neoplastic conditions, and inflammatory ailments. This comprehensive review centers on elucidating the architectural and distributive characteristics of TLR4, its conventional signaling pathways, and its mode of action in diverse disease contexts. Ultimately, this review aims to propose novel avenues and therapeutic targets for clinical intervention.

Endoplasmic reticulum (ER) stress is an evolutionarily conserved adaptive response that contributes to deal with the misfolded or unfolded protein in the lumen of the ER and restore the ER homeostasis. However, excessive and prolonged ER stress can trigger the cell-death signaling pathway which causes cell death, usually in the form of apoptosis. It is generally accepted that inappropriate cellular apoptosis and a series of the subsequent inflammatory response and oxidative stress can cause disturbance of normal physiological functions and organ damage. A lot of evidence shows that the excessive activation of the ER stress contributes to the pathogenesis of many kinds of diseases and inhibiting the inappropriate stress is of great significance for maintaining the normal physiological function. In recent years, Sirtuin1 (SIRT1) has become a research hotspot on ER stress. As a master regulator of ER stress, increasing evidence suggests that SIRT1 plays a positive role in a variety of ER stress-induced organ damage via multiple mechanisms, including inhibiting cellular apoptosis and promoting autophagy. Furthermore, a lot of factors have shown effective regulation of SIRT1, which indicates the feasibility of treating SIRT1 as a target for the treatment of ER stress-related diseases. We summarize and reveal the molecular mechanisms underlying the protective effect of SIRT1 in multiple ER stress-mediated organ damage in this review. We also summed up the possible adjustment mechanism of SIRT1, which provides a theoretical basis for the treatment of ER stress-related diseases.