Introduction: Peptidyl arginine deiminase 4 (PAD4) is an enzyme that plays an important role in gene expression, turning out genetic code into functional products in the body. It is involved in a key post translational modification, which involves the conversion of arginine to citrulline. It regulates various processes such as apoptosis, innate immunity and pluripotency, while its dysregulation has a great impact on the genesis of various diseases. Over the last few years PAD4 has emerged as a potential therapeutic target for the treatment of rheumatoid arthritis (RA).Areas covered: In this review, we discuss the basic structure and function of PAD4, along with the role of altered PAD4 activity in the onset of RA and other maladies. We also elucidate the role of PAD4 variants in etiology of RA among several ethnic groups and the current pre-clinical inhibitors to regulate PAD4.Expert opinion: Citrullination has a crucial role in RA and several other disorders. Since PAD4 is an initiator of the citrullination, it is an important therapeutic target for inflammatory diseases. Therefore, an in depth knowledge of the roles and activity of PAD4 is required to explore more effective ways to conquer PAD4 related ailments, especially RA.