LHFPL6 (LHFPL tetraspan subfamily member 6) is a transmembrane protein with emerging roles in multiple biological processes. At the blood-brain barrier, LHFPL6 functions as a component of a proton-coupled organic cation (H+/OC) antiporter that mediates transport of CNS drugs across the blood-brain barrier 1, 2. Gene knockdown studies demonstrate that LHFPL6 contributes to a TM7SF3-dependent, low-capacity transport pathway for substrates like pyrilamine 1. In Alzheimer's disease pharmacogenetics, LHFPL6 is among the most frequently mutated genes in AD patients (52.63%), accumulating pathogenic variants that may influence drug response and disease susceptibility 3. LHFPL6 has been identified as a shared causal gene linking severe COVID-19 to ischemic stroke risk, operating through immune-related and renin-angiotensin-aldosterone system pathways 4. In cancer biology, LHFPL6 serves as a cancer-associated fibroblast (CAF)-specific prognostic biomarker in colorectal cancer, with higher expression correlating with worse survival outcomes and enrichment in extracellular matrix remodeling and epithelial-mesenchymal transition pathways 5. Additionally, LHFPL6 has been associated with lipoedema susceptibility in genome-wide association studies 6. These findings suggest LHFPL6 participates in drug transport, immune regulation, stromal remodeling, and adipose tissue pathology.