Due to their pleiotropic effects on mammalian physiology a base mode of action common to all cells has been postulated. This functional link may be the modulation of the physical properties of biological membranes via alteration of membrane lipid composition. In fact, changes in the fatty acid composition of immune cell membranes have been shown to exert impact on phagocytosis, T cell signaling as well as antigen presentation. Due to the significance of lipid interactions for the formation of membrane domains, PUFAs have been speculated to perturb structure, organization and function of rafts. Moreover, Gefitinib domain structure and composition have been hypothesized to directly reflect biochemical and physiological processes. Besides, studies concerning the effects of PUFAs from the n-3 family, as eicosapentaenoic acid and docosahexaenoic acid, on immune cell function proposed a selective displacement of acylated proteins from membrane rafts by virtue of a modified raft lipid environment. In this systematic study we present fatty acid and peptide profiles of plasma membrane and rafts of macrophages from the murine cell line RAW264.7 that have been supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6 and the n-9 family. The cellular prion protein is expressed in cells of various origins. It is conserved through the whole vertebrae class, suggesting its importance in cellular physiology. However, its role in physiological processes remains enigmatic although PrPC plays a basic role in the pathogenesis of the fatal neurodegenerative disorders known as Transmissible Spongiform Encephalopathies. Observation of PrPC deficient mice did not reveal significant health problems. On the other hand, experiments in cell cultures suggested that PrPC is linked to such processes as the prevention of apoptosis, copper metabolism linked to oxidative stress, iron metabolism, signalization and differentiation. A connection between prion pathogenesis and erythropoiesis was suggested by the downregulation of the ahemoglobin stabilizing protein mRNA during prion disease. A later study indicated that the disease progression affected the transcription of several other murine erythroid genes, e.g., Kell, GPA, band 3 and ankyrin. The role of PrPC in cellular physiology has been proposed for a variety of processes, but with no prevailing consensus to date. The downregulation of erythroid genes during prion infection has established a link between the peripheral pathogenesis of prion diseases and erythropoiesis. However, it is not clear if the effect is caused by direct interaction of prion particles with erythroid cells or if it is triggered by some yet unknown humoral response to the infection. The expression of PrPC on circulating red blood cells of closely related nonhuman primates varies from several thousand per cell to zero, implying that its function on mature erythrocytes is not conserved. Griffiths et al. demonstrated the regulation of PrPC expression during the differentiation of cultured human erythroblasts in vitro, indicating that it may play a role in the differentiation of erythroid precursors.