2025 Stress Proteins in Growth, Development and Disease Gordon Research Conference and Gordon Research Seminar - PROJECT SUMMARY Protein homeostasis (often referred to as proteostasis) is the equilibrium in our cells between the timely making and degradation of proteins to ensure function and to avoid accumulation of toxic species. Both the continuously changing normal physiology and a manifold of external challenges, including acute forms of stress (temperature, oxidation and inflammation) or chronic conditions (expression proteins from inherited gene mutations or due to somatic mutations during aging) require a highly orchestrated and versatile protein quality control systems that ensures that this balance is well-maintained. This network not only concerns chaperones and protein degradation systems (both proteasomal and lysosomal) that assist in folding and disposal, but also coordinated regulation of the making or halting of protein synthesis (both at the transcriptional and translational level). Importantly, if protein homeostasis collapses, a progressive cascade of protein aggregation is initiated driving the age-related decline in cellular functions and degeneration of tissues, ultimately leading to loss of organismal resilience. Whilst protein aggregation is best known as the driver of neurodegenerative diseases, it is becoming clear that it is also a root cause for several other age-related diseases including cardiomyopathies, muscular dystrophies and type-2 diabetes. Inversely, the adaptive capacity of cells to restore imbalances in the making of (faulty) proteins by adjusting their protein quality control systems sustains their vitality during carcinogenesis. The 2025 GRC on Stress Proteins in Growth, Development and Disease , scheduled for July 6-11, 2025, at the Jordan Hotel at Sunday River. This 12th installment will be held under the subtitle “Targeting the integrated PQC network to combat ageing and age-related diseases” and promises to cover the cutting edge advances in the field of protein homeostasis, ranging from the basic regulatory mechanisms that drive their versatile and adaptive response to changing conditions, to how components of protein quality control systems act at the molecular level to handle (misfolded) proteins, up to (pharmacological) intervention strategies that boost or inhibit these systems to combat (age-related) diseases to improve healthy aging. The conference will begin with the Graduate Research Seminar (GRS) on July 5-6, nurturing the next generation of investigators in our field. Exceptional GRS participants, selected by the GRS attendees, will showcase their research through oral presentations at the main conference. Moreover, dedicated sessions and roundtable discussions will empower junior investigators, emphasizing inclusivity and diversity in scientific pursuits. Finally, a PowerHour session, focused on diversity, will complete this conference. Our meetings have always blended cutting-edge science, on a deeper understanding of the maintenance of protein homeostasis, with a warm and inclusive atmosphere, fostering collaborations and invaluable connections for future careers. Led by Dr. Harm H. Kampinga (chair) and Dr. Patricija van Oosten- Hawl (co-chair), this GRC promises to uphold its reputation as a premier gathering in the field, charting the course for future advancements in protein homeostasis research.