We examine the common features of the JNK protein structure and the possibilities of discovering JNK-isoform-specific inhibitors since, although JNK1 and JNK2 are involved in multiple diseases, including cancer, obesity, diabetes, musculoskeletal and liver disease, no cell-specific or isoform-specific inhibitors are available. Here, MAPK8 is linked to obesity due to melanocortin 4 receptor deficiency.