FAM237A (family with sequence similarity 237 member A) is a neuropeptide that functions as an endogenous agonist for the orphan G protein-coupled receptor GPR83. The protein is produced as an inactive precursor requiring posttranslational processing to generate a mature, C-terminally cleaved and amidated 9 kDa secreted form 1. This mature FAM237A binds to GPR83 with nanomolar affinity and activates the receptor with nanomolar efficiency, inducing receptor internalization and β-arrestin recruitment 2. FAM237A is the primary endogenous ligand for GPR83, with the paralog FAM237B also capable of activating this receptor at nanomolar concentrations, though with reduced potency 3. GPR83 is primarily expressed in the brain where it regulates energy metabolism and anxiety-related behaviors 2. The clarification of FAM237A as a bona fide GPR83 ligand provides a foundation for investigating the functional roles of this brain-specific receptor system and the previously understudied neuropeptide FAM237A in central nervous system physiology and potentially regulatory T-cell function.