We request partial support for the 2008, 2010 and 2012 Federation of American Society of Experimental Biologists (FASEB) Summer Conference on "Protein Folding in the Cell". The 2008 meeting will be held July 27 to August 1, 2008 in Saxtons River, VT. This extraordinarily successful meeting is unique in bringing together cell biologists/geneticists, biophysicists/biochemists, and mathematical modelers to tackle the complex problems of protein folding and misfolding and their implications for human disease. The extent to which this meeting is central to the development of the field cannot be overestimated. Historically, biophysical chemists who study protein folding and cell biologists concerned with protein biogenesis in vivo have not interacted extensively;however the complexity of the biological problems requires understanding mechanism as well as cellular function. Now, more than ever, biologists are approaching mechanism while the theorists are seeking ties to biological function. This is the meeting that brings together cutting edge research from diverse fields to allow for cross-fertilization of ideas. The vitality of this meeting is attested to by the fact that it is always oversubscribed with a constant stream of new people wishing to join the meeting. Each meeting maintains our core focus on in vivo and in vitro mechanisms of protein folding and how they relate to basic processes in cell biology, gene regulation and human disease, while devoting considerable attention to new developments. Thus, in 2008 about half of the program deals with the enduring themes of protein folding and the molecular machines that carry out this process, as well as diseases resulting from protein misfolding and the other half considers the new themes of folding of single molecules, the rapid progress in understanding folding in different cellular compartments and locations, and emerging technologies. Our goal through this meeting is to bring together physical and biological scientists in an interactive environment, to promote education and understanding of the approaches, experimental limitations and to explore common interests. The small size and isolated setting of this meeting with all participants residing and taking their meals in close proximity promotes optimal scientific exchange. The conference format will provide extensive arenas for informal discussions. Poster sessions will allow all participants to interact scientifically with other investigators. Young investigators and women are well-represented among speakers and encouraged to attend the conference and we propose strategies to increase the number of minority participants.