Listeria monocytogenes is a common clinical pathogen primarily transmitted among humans and animals through contaminated food. Currently, the increasing prevalence of antibiotic resistance due to the misuse of antibiotics has become a significant problem, leaving both clinical medicine and agriculture with a lack of effective treatments for Listeria infections. Listeriolysin O (LLO), a virulence factor secreted by Listeria monocytogenes, is a key factor in its pathogenicity. Strains of Listeria monocytogenes lacking the LLO gene are non-pathogenic to humans and animals. Therefore, studying the molecular mechanisms of LLO degradation is of great practical significance for treating clinical infections caused by antibiotic-resistant Listeria. Additionally, it will provide a theoretical basis for developing new antimicrobial drugs. Since Listeria monocytogenes secretes LLO throughout its entire life cycle within the host cell, understanding the fate of LLO at different stages of infection is crucial for elucidating the pathogenic mechanisms of Listeria monocytogenes. It is already known that LLO secreted by Listeria within the phagosome can be degraded via the lysosomal pathway. However, the fate of LLO secreted by Listeria in the cytoplasm remains poorly understood. Based on our previous experimental data and relevant literature, we propose a novel hypothesis that the AP-2 complex targets and degrades LLO secreted by Listeria in the cytoplasm.