Smoothened Receptor (SMO)

Smoothened (SMO) is a G protein-coupled receptor (GPCR) belonging to the Class Frizzled (Class F) family. It is a critical component of the Hedgehog (Hh) signaling pathway, which plays essential roles in embryonic development, tissue patterning, and adult tissue homeostasis. In its inactive state, SMO activity is suppressed by another transmembrane receptor called Patched (PTCH), which prevents inappropriate activation of Hh signaling. Upon binding of Hedgehog ligands to PTCH, this inhibition is relieved, allowing SMO to activate downstream effectors and ultimately regulate target gene expression. Dysregulation or mutation of components in this pathway—including activating mutations in SMO or loss-of-function mutations in PTCH—can lead to developmental disorders and various cancers such as basal cell carcinoma and medulloblastoma.

Activation of the Hedgehog pathway via direct binding to Smoothened independently of PTCH inhibition (SAG). Inhibition of Smoothened function (Cyclopamine, Vismodegib).