In the past century the medical sciences have made great strides in diagnostics by using a reductionist approach. Complex disease phenotypes have been meticulously dissected molecularly often resulting in clear genetic definitions. However, the development of therapies is lagging behind our ability to screen and diagnose these diseases in the lab. One reason for the lag in therapy development may be that our enhanced diagnostic capacity has led to the definition of many orphan diseases; afflictions that affect only a small number of people. Therefore it may be time for a more holistic approach; an investigation of systems as a whole, which Systems biology tries to achieve. Science needs to look for commonalities between disease mechanisms wherever possible to enhance the chance of finding common footholds for therapies that target multiple diseases. Unraveling further molecular interactions and their localizations in muscle would provide access to potential protein networks that underlie the individual forms of LGMD. An overlap between these networks may provide further unification of the disease. The newly discovered interactions may provide a different basis for extending the molecular networks in muscle maintenance and LGMD pathogenicity. Moreover, they may provide new therapeutic perspectives by focusing on similarities instead of differences.