Old dogs-new tricks: multifaceted functions of MAVS beyond antivirus activity in human health and diseases

Mitochondrial Antiviral Signaling Protein (MAVS), a key adaptor in the innate immune system, has traditionally been recognized for its role in defending against viral infections through activation of the interferon (IFN) and NF-κB signaling pathways. Recent studies, however, have expanded this view, revealing that MAVS also functions at the intersection of innate immunity, mitochondrial dynamics, and cellular metabolism. Located on the outer mitochondrial membrane, MAVS serves as a critical signaling hub, linking pathogen detection to inflammatory and stress responses. Beyond its canonical antiviral roles, MAVS is now implicated in diverse physiological and pathological processes, including regulation of apoptosis, NLRP3 inflammasome activation, metabolic reprogramming, and autophagy. Its dysregulation contributes to the onset and progression of a range of diseases, such as cancer, cardiovascular and autoimmune disorders, and neurological conditions. This review provides a comprehensive overview of MAVS activation, downstream signaling outputs, and regulatory mechanisms. We also discuss the emerging evidence on MAVS-related diseases and therapeutic strategies targeting MAVS, emphasizing its broader significance in human health beyond antiviral immunity.