Summary/Abstract The 2022 FASEB Summer Research Conference on Ubiquitin & Ub-like proteins: Cell Functions and Therapeutic Targeting will be held at the Southbridge Hotel and Conference Center, Southbridge, Massachusetts, July 24th to July 28th, 2022. This FASEB-sponsored conference has been held biannually since 1989; this application seeks support for the 2022 conference, which was delayed due to COVID-19 from 2020. The conference will bring together approximately 150 investigators (junior and senior scientists, postdoctoral fellows, graduate students, and people from industry and government) for discussions of recent advances in the areas of regulated proteolysis and signaling by ubiquitin (UB) and ubiquitin-like (UBL) protein modification, with special emphasis on human diseases. Protein ubiquitination cuts across all fields of biology and the diversity of its impacts cannot be overstated. The selective degradation of proteins by the ubiquitin system is a mechanism for control of virtually all aspects of eukaryotic cell biology, including the cell cycle, transcription, metabolic pathways, development, and antigen processing. In addition, non-proteolytic functions of ubiquitination and UBL modification in protein trafficking and signaling are critical for processes that involve membrane receptors and signaling in the innate immune system, while others help to coordinate the DNA damage response. Dysfunction of the system is involved in many disease processes, particularly cancer, neurologic and developmental diseases, and viral and microbial infectious diseases. In addition, UB and UBL proteins are critical in infectious diseases, and it is now evident that microbes encode UBL proteins, that bacteria and viruses produce enzymes to modulate and/or emulate cellular ubiquitination pathways in host cells, and that cells defend themselves against infectious agents with specific UBL proteins. The topics of eight scientific sessions will be: (i) Mechanism of Ubiquitin Conjugation & Deconjugation; (ii) Molecular Machines; (iii) Disease Pathology; (iv) Ub-like Proteins and Atypical Ubiquitin; (v) Protein Quality Control and Stress; (vi) Organelles and Pathways; (vii) Therapeutic Targeting; (viii) Signaling Pathways and Cell Fate. In addition, there will be two poster sessions and a Meet the Experts discussion panel focused on career development. This conference will be a timely and important meeting in this rapidly growing research area. It is unique in that it provides a format that brings together an extraordinary range of investigators whose collective approaches encompass cell biological, biochemical, structural biology, molecular and genetic methods that address central issues in the regulation of cellular proliferation and signaling pathways. The FASEB SRC format provides a safe and inclusive environment that encourages informal and open discussions among the participants and this in turn fosters initiation of collaborative efforts and stimulates ...