Using extensive analysis of cellular and preclinical experimental models, we identified ACBP, a regulatory protein that functions both intracellularly and as a secreted factor, as a negative regulator of brown fat activity. ACBP’s influence on brown adipose tissue has significant implications for whole-body energy balance and systemic metabolism. This study is part of the PhD thesis research conducted by Albert Blasco in our laboratory. For access to article, see: https://doi.org/10.1016/j.molmet.2025.102153