HTR2A encodes the 5-hydroxytryptamine receptor 2A, a G protein-coupled serotonin receptor that mediates Gq/11-coupled signaling and intracellular calcium mobilization 1. The receptor binds serotonin and also serves as a target for hallucinogenic compounds like psilocybin and LSD, which activate its active state and mediate both therapeutic and psychoactive effects 1. Mechanistically, HTR2A activates phospholipase C-dependent signaling cascades and regulates excitatory synaptic transmission. Recent evidence demonstrates that HTR2A expression is transcriptionally regulated by Zkscan4 in the hippocampus, with reduced HTR2A expression conferring resilience to chr13 stress 2. Additionally, HTR2A mediates hepatic serotonin signaling via the gut-liver axis, where HTR2A activation promotes high-fat diet-induced hepatic steatosis 3. Clinically, HTR2A genetic variants (particularly rs6313 T102C) show modest associations with substance use disorders, especially alcohol dependence 4. However, current evidence does not support clinical use of HTR2A genotyping for antidepressant dosing 5, and associations with antipsychotic response are ethnicity- and drug-dependent 6. HTR2A's role in other psychiatric disorders remains inconsistently replicated 7. HTR2A antagonism shows therapeutic potential for nonalcoholic fatty liver disease treatment 3.