HTR2B is a G-protein coupled receptor (GPCR) for serotonin (5-HT) and ergot alkaloids that mediates critical cellular signaling 12. Ligand binding triggers conformational changes activating G(q)/G(11) proteins, which stimulate phospholipase C-beta to release second messengers (DAG and IP3), mobilizing intracellular calcium and activating PI3K/Akt/mTOR signaling 134. Beta-arrestin family members provide alternative signaling modulation 3. HTR2B regulates dopamine and serotonin neurotransmission, behavior including impulsivity, cardiac development, and bone density 5. Clinically, HTR2B dysregulation contributes to multiple cancers. In gastric adenocarcinoma, elevated HTR2B expression associates with shorter patient survival and enhanced ferroptosis resistance through PI3K/Akt/mTOR-mediated lipid metabolism reprogramming 6. In pancreatic cancer, HTR2B-LYN-p85 complex formation drives the Warburg effect under metabolic stress, promoting tumor growth 7. In colorectal cancer, HTR2B inhibition suppresses proliferation via ERK signaling suppression 8. HTR2B antagonism also sensitizes nonfunctioning pituitary adenomas to cabergoline by blocking Gαq/PLC/PKC/STAT3 signaling 9. Additionally, HTR2B polymorphisms associate with crack cocaine use disorders 10, highlighting its role in addiction vulnerability.