Padi4, also known as peptidyl arginine deiminase type 4, is an enzyme that deiminates arginine to citrulline. It functions as an epigenetic modifier and is involved in histone modification [1,5]. Padi4 has been associated with various biological processes and diseases, including tumor suppression, cancer metastasis, and rheumatoid arthritis [1,2,3,4,6,7,8,9].

In tumor-related studies, a hypomorphic variant of TP53 (Y107H) was used to identify Padi4 as a tumor-suppressive p53 target gene, and Padi4 was shown to require an intact immune system for tumor suppression [1]. In lung, gastric, and osteosarcoma cancers, Padi4 promotes epithelial-mesenchymal transition (EMT), enhancing cancer cell invasion and migration [3,4,7]. In contrast, anti-Padi4 antibody treatment can suppress breast cancer growth by inhibiting fibronectin citrullination in the tumor microenvironment [9]. In rheumatoid arthritis, Padi4 polymorphisms and haplotypes are associated with disease susceptibility in Egyptians, and a meta-analysis indicated a role in Asian populations [2,8].

In conclusion, Padi4 is an important epigenetic modifier involved in tumor suppression and cancer metastasis, as well as in the susceptibility to rheumatoid arthritis. Studies using genetic models like the Y107H hypomorphic variant in mice have been crucial in revealing Padi4's role in these disease conditions, providing potential therapeutic targets for cancer and insights into the genetic basis of rheumatoid arthritis.