Coronaviruses subvert the endolysosomal system. Coronaviruses infection reduces the acidity of lysosomes from pH 4.7 to pH 5.7 and protease activity. It further provokes lysosomal exocytosis with the release of virions and other contents, such as cathepsin D, to the extracellular environment Lysosomal exocytosis leads to the exposition of lysosomal markers such as LAMP1 at the plasma membrane. The GTPase Arl8b participates in the anterograde motility of LAMP1+ lysosomes filled with viruses. Furthermore, lysosomes of SARS-CoV-2 infected cells are positive for ORF3a, which blocks the autophagic flux in cells. In SARS-CoV-2 infected cells, late endosomes/lysosomes accumulate because ORF3a interacts with the HOPS complex inhibiting the fusion of late endosomes/lysosomes with amphisomes and autophagosomes. For a more detailed description of ORF3a action, please refer to the main text. Image created using BioRender.