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Most cell entry by invading pathogens involves penetration of either the plasma membrane or the endo-lysosomal compartment to reach the cytosol. This process frequently inflicts membrane damage and provokes a cellular response. This Autophagic Punctum summarizes our recent study investigating how adenovirus endosome penetration is recognized and activates macroautophagy/autophagy. Our key finding is that TBK1 (TANK binding kinase 1) has a dual role in the cell response to membrane damage; it is part of an immediate-acting membrane-damage-sensing complex and is a crucial driver of the resulting autophagic response. Thus, TBK1 is a central factor linking sensors and effectors during the cell response to membrane damage.