A case involving a 68-year-old female with a 20-year BCC history revealed multifocal tumor recurrence post 20 weeks of Vismodegib (150 mg/d) treatment, with sequencing uncovering novel heterozygous missense SMO mutations (c.842G > T (p. Trp281Leu) in exon 4 and c.961G > A (p. Val321Met) in exon 5).[35] Similarly, Sonidegib’s binding to SMO was observed to induce SMO mutations, promoting Sonidegib resistance.[20] Itraconazole (ITZ), another HPI, impedes SMO’s localization to cilia, thus inhibiting the Hh pathway. Here, SMO is linked to skin basal cell carcinoma.