The P2X7 receptor is a trimeric ion channel gated by extracellular adenosine 5'-triphosphate. The receptor is present on an increasing number of different cells types including stem, blood, glial, neural, ocular, bone, dental, exocrine, endothelial, muscle, renal and skin cells. The P2X7 receptor induces various downstream events in a cell-specific manner, including inflammatory molecule release, cell proliferation and death, metabolic events, and phagocytosis. As such this receptor plays important roles in heath and disease. Increasing knowledge about the P2X7 receptor has been gained from studies of, but not limited to, protein chemistry including cloning, site-directed mutagenesis, crystal structures and atomic modeling, as well as from studies of primary tissues and transgenic mice. This chapter focuses on the P2X7 receptor itself. This includes the P2RX7 gene and its products including splice and polymorphic variants. This chapter also reviews modulators of P2X7 receptor activation and inhibition, as well as the transcriptional regulation of the P2RX7 gene via its promoter and enhancer regions, and by microRNA and long-coding RNA. Furthermore, this chapter discusses the post-translational modification of the P2X7 receptor by N-linked glycosylation, adenosine 5'-diphosphate ribosylation and palmitoylation. Finally, this chapter reviews interaction partners of the P2X7 receptor, and its cellular localisation and trafficking within cells.