HCAR3 is a G-protein-coupled receptor that functions as a metabolic sensor crucial for lipid homeostasis and cellular energy regulation 1. The receptor primarily signals through inhibitory Gi/o proteins in response to the endogenous ligand 3-hydroxyoctanoate, a fatty acid β-oxidation intermediate 1. HCAR3 acts as a negative feedback regulator of adipocyte lipolysis, counterbalancing prolipolytic signals during elevated β-oxidation 1. Additionally, HCAR3 functions as a low-affinity nicotinic acid receptor at pharmacologically relevant doses 1. Beyond lipid metabolism, HCAR3 regulates epithelial cell fate decisions, controlling keratinocyte proliferation, migration, and cellular respiration through modulation of mitochondrial morphology and metabolite utilization 2. In innate immune cells, HCAR3 activation promotes anti-inflammatory responses by shifting macrophage metabolism toward reduced glycolytic phenotypes and increasing IL-10 secretion while decreasing IL-1β 3. Disease relevance includes colorectal and breast cancer, where HCAR3 variants have been identified as potential biomarkers 45. HCAR3 also emerges as a target for immunometabolic regulation and potential cancer immunomodulation through kynurenic acid signaling 6. These diverse functions establish HCAR3 as a multifunctional metabolic and immune regulator with significant therapeutic potential across metabolic and oncological diseases.