Patched-1 receptor (PTCH1)

Patched-1 receptor (PTCH1) is a 12-pass transmembrane receptor that acts as the primary receptor for Sonic Hedgehog (SHH) and other Hedgehog ligands. PTCH1 functions as a tumor suppressor by inhibiting the GPCR-like signaling protein Smoothened (SMO) in the absence of Hedgehog ligands. Upon binding of Hedgehog ligands to PTCH1, this inhibition is relieved, allowing propagation of Hedgehog signaling, which influences critical processes during embryogenesis, cell proliferation, tissue patterning, and tumorigenesis. Mutations in PTCH1 can cause constitutive activation of the Hedgehog pathway, contributing to developmental disorders and various cancers such as basal cell carcinoma and medulloblastoma. PTCH1 is a key therapeutic target in Hedgehog pathway-driven tumors, with clinical focus on indirectly targeting its pathway through SMO inhibitors.

Other names

Patched homolog 1PTCHPTCPTC1BCNSNBCCSpatched (Drosophila homolog)HPE7FLJ26746FLJ42602PTC1_HUMAN

Inhibitors relieve PTCH1-mediated suppression of Smoothened, thus activating Hedgehog pathway signaling. Some drugs (like vismodegib/sonidegib) act on Smoothened to modulate effects downstream of PTCH1 loss or mutation.