Since their discovery by de Duve, there has been great interest in the role of lysosomes in disease. Lysosomal disorders, of which more than 50 are known, are caused by defects in proteins critical to lysosomal function and are typically characterized by substrate accumulation in various parts of the endosomal-lysosomal-autophagosomal system. Despite years of study of the genetic and molecular bases of these disorders, and the advancement of new therapies (e.g., enzyme replacement and substrate reduction therapies), precisely how disease cascades emanating from lysosomal dysfunction lead to cell dysfunction and clinical disease has remained poorly understood. This third Gordon Research Conference on Lysosomal Disease follows a successful second meeting in Lucca (Barga), Italy and moves back to its original U.S. site, the historic Hotel Galvez in Galveston, Texas. This meeting will also mark the 60th anniversary of the development of the lysosomal disease concept by H.G. Hers in 1965. Emphasis will be placed on the burgeoning role of the greater lysosomal system as a key regulator of cell homeostasis in health and disease. Invited speakers will focus on newly emerging aspects of lysosomal biology, molecular and cellular mechanisms of pathogenesis and the relationship of lysosomal diseases to other disorders, the consequences of heterozygosity and of XCI in X-linked lysosomal disorders, new experimental therapies and experiences with ongoing clinical trials. There will also be a late-breaking topics session (with speakers chosen closer to the time of the meeting so as to include the most recent developments) and short poster talks (based on those posters generating the greatest interest during the meeting). In addition to invited speakers, each session will also have short talks with presenters chosen prior to the meeting based on abstract submissions.