FAM237B is a conserved 139 amino acid microprotein that functions as an orexigenic neuropeptide in hypothalamic neurons. Originally misannotated as a long non-coding RNA (Gm8773 in mice), FAM237B is now recognized as an evolutionarily ancient peptide present from jawless vertebrates to mammals 1. Structurally, FAM237B contains a highly conserved C-terminal region consistent with prohormone processing and produces a mature, C-terminally amidated 9 kDa secreted form 2. FAM237B functions as an endogenous agonist for the G-protein-coupled receptor GPR83, activating it at nanomolar concentrations (1-10 nM) 3. The peptide is enriched in hypothalamic NPY/AgRP (Neuropeptide Y/Agouti-related peptide) neurons, which integrate metabolic signals to control feeding 1. Expression of FAM237B is dynamically regulated by metabolic and inflammatory states: fasting and serum withdrawal increase expression while insulin suppresses it via PI3K signaling 1. IGF1 also regulates Fam237b expression, contributing to an anorexigenic profile under physiological conditions 4. Additionally, pro-inflammatory cytokines (LPS, IL-6, TNF-α) robustly increase Fam237b expression 1. Intracerebroventricular administration of recombinant FAM237B exhibits orexigenic activity, promoting feeding in obese mice 5, positioning it as a key regulator of hypothalamic appetite control and energy homeostasis.