ESAT-6 is a key virulence factor in Mycobacterium tuberculosis (Mtb) that plays a critical role in TB immunopathology. It modulates the host immune response by subverting immune signaling pathways, leading to immune activation, cell death, and disease progression. ESAT-6 is secreted via the ESX-1 system and is involved in the activation of TLRs, which triggers inflammatory responses and the production of cytokines like IFN-γ and IL-1β. It also contributes to the formation of granulomas and the dissemination of Mtb by inducing necrosis and apoptosis in host cells. ESAT-6 can promote the development of Th17 cells and is a potential vaccine candidate. It is also a biomarker for TB diagnosis, as it is associated with immune responses and disease severity. ESAT-6's role in modulating autophagy and the immune system highlights its importance in TB pathogenesis. Understanding ESAT-6's mechanisms could lead to new therapeutic strategies and diagnostic tools for TB.ESAT-6 is a key virulence factor in Mycobacterium tuberculosis (Mtb) that plays a critical role in TB immunopathology. It modulates the host immune response by subverting immune signaling pathways, leading to immune activation, cell death, and disease progression. ESAT-6 is secreted via the ESX-1 system and is involved in the activation of TLRs, which triggers inflammatory responses and the production of cytokines like IFN-γ and IL-1β. It also contributes to the formation of granulomas and the dissemination of Mtb by inducing necrosis and apoptosis in host cells. ESAT-6 can promote the development of Th17 cells and is a potential vaccine candidate. It is also a biomarker for TB diagnosis, as it is associated with immune responses and disease severity. ESAT-6's role in modulating autophagy and the immune system highlights its importance in TB pathogenesis. Understanding ESAT-6's mechanisms could lead to new therapeutic strategies and diagnostic tools for TB.