As RIPK3 can regulate the death- and inflammation-inducing activity of both caspase-8 and MLKL in disease-causing macrophages (Vince et al, 2012; Lawlor et al, 2015), direct comparisons of mutant animals in the same obesity and MAFLD model are required to define their pathological roles and divergent activities. Here, RIPK3 is linked to obesity due to melanocortin 4 receptor deficiency.