c-Mpl activators represent a class of chemical compounds that interact specifically with the cellular receptor known as c-Mpl, also referred to as the thrombopoietin receptor (TPO-R). This receptor is a member of the type I cytokine receptor family and is primarily involved in the regulation of hematopoietic processes, especially in megakaryocyte and platelet production. The c-Mpl receptor is a transmembrane protein that, upon activation, initiates a cascade of intracellular signaling pathways. These pathways predominantly involve the Janus kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) axis, among other downstream signaling molecules. The activation of these pathways leads to changes in gene expression that drive cell proliferation, differentiation, and survival. Importantly, c-Mpl activators are not limited to proteins like thrombopoietin; small molecule activators and peptide mimetics have also been identified, which can effectively modulate the receptor's activity.The structural diversity of c-Mpl activators is broad, encompassing both natural ligands like thrombopoietin and synthetic molecules designed to mimic or enhance the receptor's activation. These activators typically engage the receptor by binding to its extracellular domain, inducing conformational changes that propagate through the transmembrane domain to the intracellular signaling regions. The precise mechanism by which these activators modulate the receptor function can vary; some may induce full activation of the receptor, while others may act as partial agonists, selectively triggering certain signaling pathways over others. Additionally, research into c-Mpl activators has revealed insights into the receptor's structural biology, offering a deeper understanding of how ligand binding translates into specific cellular responses. This knowledge has implications for studying how signal transduction is regulated within hematopoietic cells, providing a basis for exploring the fundamental biological roles of c-Mpl in various physiological processes.