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While the mechanism for FAD incorporation into PPOX is unknown, potential interactions between FAD synthases and apo-flavoproteins may facilitate the chaperoning of FAD into the apoenzyme as FAD is being synthesized ( In vertebrate erythroid cells, full PPOX activity requires CLPX, a mitochondrial protein unfoldase, but not CLPP, the proteolytic subunit of the CLPXP protease (Rondelli et al., 2021), suggesting that the CLPX unfoldase has a protease-independent function in regulating heme synthesis