Although SPX was discovered over 15 years ago, the manuscript of Walewski et al. from 2014 is considered a breakthrough in defining its function, in which they proved that the concentration of this peptide is reduced in obesity and that the gene encoding SPX is one of the most strongly downregulated genes in the tissue fat of obese people [1,2]. Here, SPX is linked to obesity due to melanocortin 4 receptor deficiency.