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Natural killer (NK) cell–mediated killing involves the membrane fusion of preformed lytic granules. While the roles of actin and microtubules are well accepted during this process, the function of septins, another cytoskeletal component that associates with actin and microtubules, has not been investigated. Here we show that genetic depletion or pharmacologic stabilization of the septin cytoskeleton significantly inhibited NK cell cytotoxicity. Although the stabilization of septin filamentsdoi:10.1083/jcb.202002145 pmid:32841357 fatcat:s5ovwfc6ofdmjmruhtelp3zowm