Brown adipose tissue (BAT) is a highly dynamic and metabolically active organ that continuously adapts to changing nutrient availability and thermogenic demands. These adaptations place substantial stress on cellular protein quality control systems, particularly the ubiquitin–proteasome system (UPS), which regulates protein turnover through ubiquitination, yet the specific molecular components involved remain poorly understood. This project investigates the UPS in the regulation of thermogenic adipocyte biology. We will define its role in cellular energy metabolism using human primary and iPSC-derived brown adipocytes, characterize its molecular function in proteostasis by identifying interaction partners and proteomic changes, and assess its physiological relevance in transgenic mouse models during cold exposure and obesity. Finally, we have identified rare human genetic variants linked to UPS and we will study their impact in BAT organoids. Together, these studies will reveal how UPS integrates protein quality control with thermogenic function and energy metabolism.