Although the role of upstream kinases RIPK1 and RIPK3 in obesity and MAFLD remain debatable (Afonso et al, 2015, 2021; Gautheron et al, 2016; Roychowdhury et al, 2016; Karunakaran et al, 2020; Majdi et al, 2020; Tao et al, 2021), there are numerous reports that MLKL deficiency protects mice from MAFLD (Saeed et al, 2019; Xu et al, 2019; Wu et al, 2020). This evidence concerns the gene RIPK3 and obesity due to melanocortin 4 receptor deficiency.