Pannexin 1 (PANX1) channels mediate the release of 'find-me' signals and membrane permeability during apoptosis. The study identifies PANX1 as a key mediator of nucleotide release (ATP and UTP) from apoptotic cells, which is essential for recruiting phagocytes. Pharmacological inhibition and siRNA knockdown of PANX1 reduced nucleotide release and monocyte recruitment, while overexpression enhanced these processes. Patch-clamp recordings showed that PANX1 is basally inactive but becomes active during apoptosis. Mechanistically, PANX1 is cleaved by effector caspases (caspases 3 and 7), and a specific cleavage site is essential for its function during apoptosis. Truncated PANX1, which lacks this cleavage site, forms a constitutively open channel. PANX1 is also important for selective plasma membrane permeability of early apoptotic cells to specific dyes, such as YO-PRO-1 and TO-PRO-3. These findings suggest that PANX1 is a plasma membrane channel that mediates the regulated release of 'find-me' signals and selective plasma membrane permeability during apoptosis, and that caspases activate PANX1 through cleavage. The study also shows that PANX1 is a target of caspase-mediated cleavage, and that the cleavage site B is essential for PANX1 function during apoptosis. These results highlight a new mechanism of PANX1 activation by caspases and provide insights into the physiological role of PANX1 in apoptosis. The study also demonstrates that PANX1 contributes to plasma membrane permeability during apoptosis, which is relevant for the selective uptake of dyes by early apoptotic cells. The findings have implications for understanding how apoptotic cells modify their extracellular microenvironment through the selective release of molecules. The study also suggests that the cleavage of PANX1 at site B is necessary and sufficient to activate the channel, defining a new mechanism for the regulation of pannexin channels. Overall, the study provides new insights into the role of PANX1 in apoptosis and highlights its importance in the release of 'find-me' signals and membrane permeability during apoptosis.Pannexin 1 (PANX1) channels mediate the release of 'find-me' signals and membrane permeability during apoptosis. The study identifies PANX1 as a key mediator of nucleotide release (ATP and UTP) from apoptotic cells, which is essential for recruiting phagocytes. Pharmacological inhibition and siRNA knockdown of PANX1 reduced nucleotide release and monocyte recruitment, while overexpression enhanced these processes. Patch-clamp recordings showed that PANX1 is basally inactive but becomes active during apoptosis. Mechanistically, PANX1 is cleaved by effector caspases (caspases 3 and 7), and a specific cleavage site is essential for its function during apoptosis. Truncated PANX1, which lacks this cleavage site, forms a constitutively open channel. PANX1 is also important for selective plasma membrane permeability of early apoptotic cells to specific dyes, such as YO-PRO-1 and TO-PRO-3. These findings suggest that PANX1 is a plasma membrane channel that mediates the regulated release of 'find-me' signals and selective plasma membrane permeability during apoptosis, and that caspases activate PANX1 through cleavage. The study also shows that PANX1 is a target of caspase-mediated cleavage, and that the cleavage site B is essential for PANX1 function during apoptosis. These results highlight a new mechanism of PANX1 activation by caspases and provide insights into the physiological role of PANX1 in apoptosis. The study also demonstrates that PANX1 contributes to plasma membrane permeability during apoptosis, which is relevant for the selective uptake of dyes by early apoptotic cells. The findings have implications for understanding how apoptotic cells modify their extracellular microenvironment through the selective release of molecules. The study also suggests that the cleavage of PANX1 at site B is necessary and sufficient to activate the channel, defining a new mechanism for the regulation of pannexin channels. Overall, the study provides new insights into the role of PANX1 in apoptosis and highlights its importance in the release of 'find-me' signals and membrane permeability during apoptosis.