As a special feature, PDAC generally requires highly active cholesterol metabolism to survive and grow, though the in‐depth mechanistic understanding remains elusive.[14a,d] In RNF43‐mutant PDAC, Fzd5‐mediated Wnt/β‐catenin activity is required for tumor survival and growth.[5b] We thus proposed that Fzd5 may act as a critical “bridge” to couple aberrant cholesterol metabolism with Wnt signaling in RNF43‐mutant PDAC. The gene discussed is RNF43; the disease is neoplasm.