With the increasing prevalence of obesity‐associated metabolic and cardiovascular disorders, our study places the lipid kinase PIKfyve in the context of cardiometabolic diseases and highlights the therapeutic potential of PIKfyve pharmacological inhibition to limit mitochondrial damage and to improve cardiometabolic phenotype in obese patients. This evidence concerns the gene PIKFYVE and obesity due to melanocortin 4 receptor deficiency.