PTCH

PTCH, also known as Patched, is a transmembrane protein that acts as a receptor for the Hedgehog signaling pathway. It is a crucial component in the regulation of cell growth, differentiation, and tissue patterning during embryonic development. PTCH functions by binding to Sonic hedgehog (Shh) and other Hedgehog ligands, thereby inhibiting the activity of another transmembrane protein called Smoothened (Smo). In its unbound state, PTCH restricts Smo localization and prevents the activation of downstream transcription factors like Gli. When a Hedgehog ligand binds to PTCH, this inhibition is relieved, allowing Smo to accumulate in the primary cilium and initiate the downstream signaling cascade.

Mutations in the PTCH gene are implicated in various developmental abnormalities and cancers. In humans, germline mutations in PTCH1 are the primary cause of nevoid basal cell carcinoma syndrome (NBCC), also known as Gorlin syndrome. This autosomal dominant disorder is characterized by a predisposition to develop multiple basal cell carcinomas, medulloblastomas, and other tumors. Somatic mutations in PTCH1 are also frequently observed in sporadic basal cell carcinomas and other cancers, highlighting its role as a tumor suppressor. The precise mechanisms by which PTCH dysfunction leads to tumorigenesis are complex and involve dysregulation of cell proliferation and survival pathways.