Additionally, once demonstrated the validity and specificity of our protocol, we provide evidence of the applicability and advantages of detecting pMLKL-S345 in situ by utilising three additional models that uncover, clarify and support (1) the role of necroptosis in SARS-CoV infection, (2) the role of RIPK3 in inflammation independently of MLKL via the analysis of the chronic proliferative dermatitis mutation (cpdm) mice (Sharpincpdm/cpdm) and Sharpincpdm/cpdm; Ripk3−/− animals and (3) the role of necroptosis in systemic inflammatory response syndrome (SIRS) following TNF injection. The gene discussed is TNF; the disease is systemic inflammatory response syndrome.