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Protein arginine deiminase 6 (PAD6) is a homodimeric guanidine-modifying enzyme belonging to the amidinotransferase superfamily.{34555} It is a calcium-dependent enzyme that catalyzes the post-translational modification of target proteins by converting arginine to citrulline. PAD6 is expressed in mammalian oocytes, sperm cells, and early embryos.{39678} In mammalian oocytes and early embryo cytoplasm, its expression is localized to cytoskeletal sheets, dynamic structures containing various keratins, which are major targets for citrullination. PAD6-/- oocytes exhibit reduced microtubule acetylation and defective organelle positioning and redistribution, suggesting a role for PAD6 in regulating microtubule-mediated organelle movement and positioning.{39677} PAD6-/- female, but not male, mice are infertile due to a reduction of de novo protein synthesis, cytoskeletal sheet formation, and ribosomal RNA which induces arrest of zygote development at the two-cell stage.{39678,39679} PAD6 is regulated by newborn ovary homeobox (Nobox), as its promoter contains a Nobox DNA-binding element (NBE) and expression and activity of PAD6 are decreased in Nobox-/- mouse ovaries.{39676} In human females, homozygous nonsense mutations and compound-heterozygous mutations in PAD6 induce early embryonic arrest following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).{39680}