Hydroxycarboxylic acid receptor 1 (HCA<sub>1</sub>), formerly known as G protein-coupled receptor 81 (GPR81), is a protein that in humans is encoded by the HCAR1 gene. HCA<sub>1</sub>, like the other hydroxycarboxylic acid receptors HCA<sub>2</sub> and HCA<sub>3</sub>, is a G protein-coupled receptor (GPCR). The primary endogenous agonist of HCA<sub>1</sub> is lactic acid (and its conjugate base, lactate). More recently, 3,5-dihydroxybenzoic acid has been reported to activate HCA<sub>1</sub>.
Lactate was initially found to activate HCA<sub>1</sub> on fat cells and thereby to inhibit these cells lipolysis i.e., break-down of their fats into free fatty acids and glycerol. Subsequent studies have found that in addition to fat cells, HCA<sub>1</sub> is expressed on cells in the brain, skeletal muscle, lymphoid tissue, uterus, kidney, liver, and pancreas as well as on immune cells such as macrophages and antigen-presenting cells. In the brain, HCA<sub>1</sub> acts to dampen neuron excitation and may also function to promote neurogenesis (the production of neurons from neural stem cells) and angiogenesis (the formation of new blood vessels from pre-existing blood vessels). The functions of HCA<sub>1</sub> in non-fat and non-neural tissues have not been fully defined but in many cases appear to involve promoting the survival of cells, including various types of cancer cells.