GPR101 is an orphan G protein-coupled receptor (GPCR) of the rhodopsin-like family predominantly expressed in the hypothalamus and pituitary 1. As a class A GPCR, it couples to both Gαs and Gαi proteins, activating adenylyl cyclase-mediated signaling pathways and MAPK cascades 2. The endogenous ligand and physiological function remain unknown, though GnRH-(1-5) can activate GPR101 in vitro 2. GPR101 duplication on chromosome X.3 causes X-linked acrogigantism (XLAG), characterized by early-onset growth hormone excess and pituitary hyperplasia or adenoma 12. Increased hypothalamic GHRH secretion may contribute to pathogenesis 1. Point mutations, particularly c.924G>C (E308D) in the third intracellular loop, are associated with sporadic acromegaly and pituitary tumors 2. Additionally, GPR101 duplications can contribute to familial isolated pituitary adenomas (FIPA) presenting with pituitary gigantism 34. Clinically, pituitary tumors associated with GPR101 alterations present earlier, grow more aggressively, and show greater resistance to medical therapy compared to sporadic adenomas, requiring complex multimodal treatment approaches 3. The role of GPR101 in growth, puberty, and appetite regulation remains under investigation 4.