The Citrullinating Enzyme PADI4 Governs Progenitor Cell Proliferation and Translation in Developing Hair Follicles

September 2025 in “ Science Advances ”

Kim Vikhe Patil, Nil Campamà Sanz, Kylie Hin-Man Mak, Wei Yang, Karl Annusver, Jasson Makkar, David Grommisch, Li Lei, Priyanka Sharma, Ryan R. Driskell, Maria Kasper, Maria Genander

PADI4 citrullination progenitor cell proliferation hair follicle development peptidylarginine citrulline mRNA processing ribosomal biogenesis protein synthesis ribosomal RNA transcription 4E-BP1 translational repressor posttranslational modifications

This study investigates the role of the enzyme PADI4 in hair follicle development, highlighting its function as a negative regulator of progenitor cell proliferation. PADI4, which converts peptidylarginine to citrulline, is found in both progenitor and differentiated hair lineage cells and represses transcription during hair follicle development. The enzyme citrullinates proteins involved in mRNA processing and ribosomal biogenesis, and its absence enhances protein synthesis and ribosomal RNA transcription. Additionally, PADI4 modifies the translational repressor 4E-BP1, indicating a regulatory interaction between PADI4 activity and 4E-BP1 phosphorylation. This research provides insights into how posttranslational modifications influence progenitor cell states and tissue formation.

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PAD enzymes play a key role in hair growth and structure.

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