The invention discloses polypeptides (Unc-51 kinase, ROMA1, and/or 2TM protein) affecting the activity of Uncoupling Proteins (UCPs), thereby leading to an altered mitochondrial activity and thus contributing to membrane stability and/or function of organelles, preferably mitochondria. This invention relates to the use of these polypepetides in the diagnosis, study, prevention, and treatment of diseases and disorders, for example, but not limited to, metabolic diseases such as obesity, adipositas, eating disorders, wasting syndromes (cachexia), pancreatic dysfunctions (for example diabetes), disorders related to ROS production, and others.