GPR155 (LYCHOS) is a lysosomal cholesterol sensor that regulates mTORC1 signaling, a master growth regulator. The protein functions as a cholesterol-binding transmembrane protein with a unique hybrid architecture combining a plant-like auxin transporter domain fused to a GPCR domain 1. In the presence of cholesterol, GPR155 binds cholesterol through a conserved motif positioned between these domains 2, causing conformational rearrangement that sequesters the GATOR1 complex and promotes mTORC1 recruitment to lysosomes 3. Conversely, during cholesterol starvation, GPR155 cannot disrupt GATOR1-KICSTOR association, leading to mTORC1 inhibition 3. Beyond cholesterol sensing, GPR155 binds indole-3-acetic acid and may participate in tryptophan metabolism 1. Clinically, GPR155 downregulation is associated with gastric cancer progression and hematogenous metastasis, with reduced expression independently predicting metastasis risk 4. In the tumor microenvironment, oxysterol metabolites compete with cholesterol for GPR155 binding, inhibiting mTORC1 and reprogramming macrophage immunosuppressive function 5. Additionally, circular RNA regulatory networks controlling GPR155 expression modulate gastric adenocarcinoma malignancy 6. These findings establish GPR155 as an immunometabolic checkpoint with therapeutic potential.