Severe acute respiratory syndrome-associated coronavirus type 1 (SARS-CoV-1) open reading frame-3a has been implicated in host cell death pathways. Receptor interacting serine/threonine protein kinase 3 (RIPK3) was found to induce oligomerization of SARS-CoV-1 3a after co-transfection of viral 3a and RIPK3 in human embryonic kidney 293 (HEK293) that do not express endogenous RIPK3 or MLKL (Yue Y et al. 2018). Confocal imaging showed that co-expressed SARS-CoV-1 3a and RIPK3 co-localized with lysosomal-associated membrane protein 1 (LAMP1) in HeLa cells (Yue Y et al. 2018). Quantification of colocalization revealed that 3a likely targets RIPK3 to lysosomes. Further, a lysosomal galectin puncta assay showed that SARS-CoV-1 3a caused lysosomal membrane permeabilization. In addition, the SARS-CoV-1 3a-mediated release of cathepsins from lysosomes in HEK293 cells (Yue Y et al. 2018). Thus, RIPK3 is thought to induce oligomerization of SARS-CoV-1 3a, which facilitates membrane insertion and ion channel functionality of SARS-CoV-1 3a (Yue Y et al. 2018).