Collectively, our data show expression patterns of PKP2 in adipose tissue mostly related to obesity and adipocyte function, and indicate that this particular component of the desmosome not only represents an important regulator of adipogenic stimuli, but also that the partial loss of PKP2 acts as a critical driver of a defective cell cycle in adipocytes, and the resulting deregulated adipocyte senescence in subjects with obesity. This evidence concerns the gene PKP2 and obesity due to melanocortin 4 receptor deficiency.