Because of the pivotal role of irisin/FNDC5 in obesity, insulin resistance and T2DM, we aim to evaluate a possible role of five FNDC5 polymorphisms (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) in obesity and T2DM phenotypes from Saudi Arabia, a region with a high prevalence of both conditions [20, 21]. This evidence concerns the gene FNDC5 and obesity due to melanocortin 4 receptor deficiency.