HTR4 encodes a G-protein coupled receptor for serotonin that mediates adenylate cyclase activation through Gs protein coupling 12. The receptor undergoes ligand-induced conformational changes to activate downstream signaling cascades 12. HTR4 exhibits tissue-specific expression patterns, with relatively low levels in adult lung tissue but dynamic expression during fetal lung development, predominantly in alveolar pneumocytes 3. In the nervous system, neuronal coculture induces HTR4 expression in metastatic tumor cells, facilitating early CNS adaptation in brain metastasis 4. Genome-wide association studies consistently identify HTR4 variants associated with reduced lung function and airflow obstruction risk 56. Functional validation in HTR4-null mice demonstrates increased baseline airway resistance and enhanced methacholine-induced hyperresponsiveness, supporting a causal relationship between HTR4 genetic variation and pulmonary phenotypes 7. Recent evidence indicates HTR4 mediates individual susceptibility to formaldehyde-induced respiratory injury through epigenetically-regulated expression changes 8, establishing HTR4 as a key modulator of airway physiology and environmental toxin susceptibility.