Although the necroptotic kinases, RIPK1 and RIPK3, have been studied in liver damage models (Li et al, 2021), it remains controversial as to whether antagonizing these kinases and necroptotic MLKL signaling is a valid therapeutic option in obesity-driven MAFLD/MASH, as disease outcomes differ based on the dietary intervention and genetic models used (Gautheron et al, 2014, 2016; Afonso et al, 2015, 2021; Roychowdhury et al, 2016; Saeed et al, 2018; Karunakaran et al, 2020; Tao et al, 2021; Pistorio et al, 2022). This evidence concerns the gene RIPK1 and obesity due to melanocortin 4 receptor deficiency.