SMO and skin basal cell carcinoma: Notably, targeted pathway inhibition has shown clinical success particularly in HH‐driven basal cell carcinoma (BCC) and medulloblastoma.1, 2 However, rapid and frequent development of resistance to HH inhibitors urgently calls for additional treatment options.3 Canonical HH/GLI signaling is initiated by the binding of secreted HH protein to Patched (PTCH), a transmembrane domain protein that represses HH signaling in its unliganded state by inhibiting the ciliary localization and activation of the essential HH effector Smoothened (SMO).