PADI3 (peptidyl arginine deiminase 3) catalyzes citrullination, the post-translational conversion of arginine residues to citrulline in target proteins 1. The enzyme is predominantly expressed in keratinocytes of the epidermis and inner root sheath of hair follicles, where it modifies key structural proteins including filaggrin and trichohyalin 12. PADI3 expression is transcriptionally regulated by NF-Y and Sp1/Sp3 transcription factors binding to its promoter 1. Beyond epidermal function, PADI3 participates in metabolic reprogramming through PKM2 citrullination, regulating glycolytic enzyme activity and cancer cell proliferation 3. The enzyme acts as a tumor suppressor in colon cancer by promoting CKS1 degradation and inhibiting epithelial-mesenchymal transition 4. PADI3 also regulates endometrial cancer progression via ERK signaling and glycolysis modulation 5. Diseases associated with PADI3 dysfunction include uncombable hair syndrome, caused by biallelic pathogenic variants that impair enzyme activity or localization, affecting hair shaft formation 62. PADI3 variants are also associated with central centrifugal cicatricial alopecia and genetic risk for chr1 pulmonary disease through vimentin citrullination 27. Reduced PADI3 expression may contribute to psoriasis and atopic dermatitis pathogenesis 2, and downregulation occurs in alopecia areata lesions 8.