ECSIT: Biological function and involvement in diseases.

Evolutionary conserved signaling intermediate in Toll pathways (ECSIT), a multi-functional protein, was first identified as a cytosolic adaptor protein in Toll-like receptors (TLRs) signaling-mediated innate immune responses. In the past two decades, studies have expanded the understanding of ECSIT. Nevertheless, there are still large knowledge gaps due to the inadequate number of studies regarding ECSIT, especially an overall review of ECSIT is lacking. Here, we first comprehensively summarize the biological functions of ECSIT with particular focus on innate immune responses and mitochondrial homeostasis. Cumulative studies have reinforced that ECSIT is involved in the regulation of innate immune responses through activating NF-κB signaling and potentiating the Retinoic acid-induced gene Ⅰ (RIG-Ⅰ)/ mitochondrial antiviral- signaling protein (MAVS) pathway-mediated innate antiviral immunity. In addition, ECSIT determines the mitochondrial morphology and function including mitochondrial complex Ⅰ (CⅠ) assembly, mitochondrial reactive oxygen species (mROS) production, mitochondrial membrane potential (MMP) maintenance and mitochondrial quality control. Owing to these distinct functions, ECSIT is involved in the etiology and pathology of human diseases including Alzheimer's disease (AD), cardiac hypertrophy, musculoskeletal disintegration, cancer, extranodal natural killer/T cell lymphoma (ENKTL) and ischemic stroke. Collectively, the roles and mechanisms of ECSIT under physiological and pathological conditions are critically discussed to provide a clearer view of the therapeutic potential of ECSIT.