AICD also has a direct link to lipid metabolism as it has been found to suppress the expression of the major lipoprotein receptor LRP1 and as such affect apoE/cholesterol metabolism (Liu et al., 2007) . On the other hand AICD controls expression of the alkyldihydroxyacetonephosphate-synthase which regulates plasmalogen synthesis in the cells (Grimm et al., 2011b) and reduced levels of these brain-specific lipids are characteristic of the AD brain (Han et al., 2001; Rothhaar et al., 2012) . Reduced plasmalogen levels in the AD brain might have direct effect on production of Aβ since they were shown to inhibit activity of γ-secretase (Rothhaar et al., 2012) . There is also evidence that AICD regulates sphingolipid synthesis via serine-palmitoyl transferase (Grimm et al., 2011a) , and as such may control composition of lipid rafts and APP processing. The wide range of putative AICD target genes highlights the role of APP signaling in normal brain functioning and in AD pathology. SPHINGOMYELIN The major component of lipid rafts, sphingomyelin (SM), is characteristic only for eukaryotic cells where it comprises about 10-15% of total phospholipids and even more in the brain and peripheral nervous tissue. SM and its metabolites play an important role as second messengers in signal transduction events during development, differentiation and immune response of the organisms (Nalivaeva et al., 2000; Hannun et al., 2001) . SM is essential for the activity of some types of receptors, including the α7 nicotinic receptor (Colón-Sáez and Yakel, 2011), NMDA receptors (Wheeler et al., 2009) , neurotrophic tyrosine kinase receptor type 2 (Trovò et al., 2011) , serotonin 1A receptor (Jafurulla et al., 2008) and the urokinase receptor (uPAR; Sahores et al., 2008) . It was also found Frontiers in Physiology | Membrane Physiology and Biophysics that some disease-related membrane proteins (APP, gp120, and PrP) have a common SM-recognition site which underscores the role of lipid rafts in AD, HIV, and prion diseases .