Abstract This application requests partial support for a Gordon Research Conference (GRC) on Lysosomes and Endocytosis at Proctor Academy, Andover, NH from June 19-24, 2022. Support for the associated Gordon Research Seminar (GRS) immediately preceding the GRC (June 18-19) is also requested. The Lysosomes and Endocytosis GRC has a 50+ year tradition as the preeminent scientific venue for investigators of endocytosis and lysosome biology in health and in disease. It is also highly regarded for the high level of communication between colleagues at all career levels, and for the mentorship of junior colleagues. For more than a decade now molecular mechanisms of endocytosis and for targeting of molecules to the lysosome for degradation have been the focus of this GRC. However, the field evolves rapidly, and recent advances indicate roles for the endo-lysosome and autophagy pathways in cancer, development, cytokinesis, intra- and inter- cellular signaling, immunity, metabolism, neurodegeneration and other neuronal diseases. The principal goal of the 2022 GRC is to build bridges between investigators working to elucidate molecular mechanisms and investigators of physiological aspects of the lysosome. A related goal is to raise awareness of and interest in lysosome biology outside of the field proper. Accordingly, the 2022 GRC program will embrace an exceptionally diverse cast of 28 invited speakers, favoring colleagues who have either not previously attended or presented at this GRC. Also featured are investigators who have not attended the conference for many years (e.g., >10 years) due to the evolving emphasis of their research programs on human disease; they provide a reservoir of experience regarding the application of fundamental knowledge of the endo-lysosome system to physiological questions. Areas to be addressed include the roles of the endo-lysosomal system in cancer, pathogen (including viruses) infection, nutrient sensing, the control of metabolism, and signaling between tissues. To attain the freshest program possible, nineteen speakers will be selected from submitted abstracts and one entire session will be devoted to new research directions. All attendees will be encouraged to participate in one of two poster sessions. A Gordon Research Seminar (GRS), open solely to graduate students and postdoctoral researchers, will convene one day prior to the start of the GRC. The informal atmosphere of the GRS allows trainees to build presentation and networking skills in a nurturing environment. Due to the vital importance of the endo-lysosomal system to human physiology, and the exceptional record of success of past Lysosomes and Endocytosis Gordon Research Conferences, the support of the NCI, NCATS, NIAID, NIA, NICHD, as well as other NIH institutes, will advance critical investments toward understanding lysosome biology in health and disease.