Ever since their discovery by de Duve, there has been great interest in the role of lysosomes in disease. Lysosomal storage disorders, of which more than 50 are known, are caused by defects in proteins critical to lysosomal function, which lead to intra-lysosomal accumulation of undegraded metabolites. Despite years of study of the genetic and molecular basis of lysosomal storage disorders, and the advancement of new therapies (such as enzyme replacement therapy and substrate reduction therapy) how the cascade of events emanating from lysosomal dysfunction leads to cell dysfunction and clinical disease remains poorly understood. This second Gordon Research Conference on Lysosomal Disease (the first very successful, meeting was held in Galveston, Texas in 2011) will have cutting-edge research sessions on topics ranging from the basic science of lysosomal biology to disease cascades and new therapies for specific diseases. Sessions will focus on molecular and cellular pathogenesis, the relationships of lysosomal diseases to other disorders, biomarker development, innovative approaches to therapy, and clinical trials and design. There will also be a hot topics session (with speakers chosen closer to the time of the meeting so as to include the most recent developments) and a poster session (with short poster talks selected on the basis of interest generated during these sessions). Additionally, a number of short talks will be chosen prior to the meeting based on abstract submissions. The collegial atmosphere of this Conference, as well as the opportunities for informal afternoon/evening gatherings, provides an environment in which scientists from different backgrounds may interact and which promotes cross-disciplinary collaborations in the various research areas represented.