Protein patched homolog 1 (PTCH1)

Protein patched homolog 1 (PTCH1) is a **transmembrane receptor** and member of the RND transporter superfamily that acts as the primary receptor for Hedgehog (HH) ligands, such as Sonic hedgehog (SHH)[1][2][6]. PTCH1 functions as a **tumor suppressor** by inhibiting the activity of another membrane protein, Smoothened (SMO), thereby suppressing downstream Hedgehog signaling and preventing inappropriate cell proliferation[1]. Upon binding Hedgehog ligands, PTCH1 is inactivated, relieves its inhibition on Smoothened, and allows pathway activation—crucial for embryonic development and tissue patterning[1][2][6]. Structurally, PTCH1 contains 12 transmembrane domains and characteristic extracellular domains, with structural features supporting a transporter-like function, especially for cholesterol/sterol molecules[2][3]. Pathogenic mutations in PTCH1 are frequent in basal cell carcinoma, Gorlin syndrome, and medulloblastoma, highlighting its essential role in growth regulation and cancer suppression[1]. PTCH1 status is central for clinical decisions in cancers associated with aberrant Hedgehog signaling, where SMO inhibitors such as vismodegib and sonidegib are applied therapeutically.

Other names

Patched 1PTCHPTCPTC1SLC65B1BCNSBCNS1NBCCSprotein patched homolog 1

Hedgehog pathway inhibition: Drugs typically either bind or otherwise inhibit downstream of PTCH1, usually by targeting Smoothened (SMO), the signaling protein that is negatively regulated by PTCH1[1][2]. Loss or mutation of PTCH1 leads to uncontrolled SMO activation; SMO inhibitors restore inhibition of this pathway.