PTCH1

Negative regulator of the smoothened signaling pathway, which acts as a receptor for hedgehog (SHH, IHH and DHH) morphogens. In absence of hedgehog, acts as an inhibitor of smoothened protein (SMO) by preventing SMO access to cholesterol: mechanistically, acts as a cholesterol transporter, which depeletes cholesterol from the outer leaflet of plasma membrane, thereby preventing cholesterol-binding to the extracellular CRD region of SMO. Hedgehog-binding inhibits PTCH1 cholesterol transporter activity, promoting SMO activation by cholesterol and transduction of the smoothened signaling pathway. Molecular mechanism governing cholesterol transport are still unclear: may move cholesterol from the outer to the inner leaflet of the membrane in exchange for potassium or sodium ion export in the opposite direction. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis..

Function from UniProtKB (Q13635), read 2026-09-23. CC BY 4.0.