CD28 is a critical costimulatory receptor expressed on the surface of T cells, particularly on CD4+ and CD8+ T cells, and plays a pivotal role in T cell activation, proliferation, and survival. It is a homodimer of 44kDa subunits, each containing a single immunoglobulin-like extracellular domain, and is part of the Ig superfamily. CD28 interacts with its ligands, CD80 (B7-1) and CD86 (B7-2), which are predominantly found on antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells. The engagement of CD28 with these ligands is essential for providing the second signal required for full T cell activation, which complements the antigen-specific signal delivered by the T cell receptor (TCR). CD28 signaling leads to the upregulation of IL-2 and its receptor expression, enhances T cell proliferation, and promotes the production of various cytokines, including IL-4, IL-5, IL-13, IFN-γ, and TNF. It also plays a role in the differentiation of T cells into memory phenotypes and in maintaining immune homeostasis. The absence of CD28 signaling results in reduced T cell survival and impaired antibody responses to T-dependent antigens. CD28 is thus a key regulatory point for successful B cell, macrophage, and cytotoxic T cell responses.