Fzd5, also known as Frizzled-5, is a member of the G-protein coupled receptor Fz/Smo family, which plays a significant role in the Wnt signaling pathway. It is involved in tissue morphogenesis and cellular polarity information transmission. Fzd5 specifically interacts with Wnt5A to activate the beta-catenin pathway and is implicated in various cellular processes including proliferation, DNA damage repair, and stemness maintenance. It also contributes to chromatin accessibility regulation in intestinal epithelial cells, influencing stem cell fate and lineage generation. Furthermore, Fzd5 has been shown to be essential for the activity of alveolar epithelial stem cells and can be targeted to promote regeneration after lung injury. Research has also highlighted its role in cancer growth, particularly in pancreatic ductal adenocarcinoma (PDAC), where it mediates Wnt/β-catenin signaling, which is necessary for tumor survival and growth. Fzd5's function is intricately linked to cholesterol metabolism, as it can bind cholesterol, affecting its maturation and transport to the cell membrane, and this interaction is crucial for its signaling role.