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In this issue of Cell, Ma et al. reveal a mechanistic role for PIEZO1 in iron homeostasis through molecular genetic mouse studies. They also demonstrate implications for human iron overload and deficiency syndromes, susceptibility to malarial infection, and red blood cell turnover in persons of African ancestries.The fin-to-limb transition has long fascinated evolutionary biologists, but a unifying theory as to its developmental origins has remained elusive. New work by Hawkins and colleagues demonstrates the surprising potential of teleost