With the advent of proteomic techniques the number of known post translational modifications (PTMs) affecting red cell membrane proteins is rapidly growing but the understanding of their role under physiological and pathological conditions is incompletely established.In erythrocytes, the central role of post translational modifications (PTMs) in the regulation of membrane functions is based on their lack of regulation by gene expression in response to physiological stimuli and cellular stresses.

Oxidative events involving band 3 (Anion Exchanger 1) the more represented RBC integral membrane protein, comprising 25% of the total membrane protein, have been associated with red blood cells (RBCs) removal through binding of naturally occurring antibodies (NAbs), in addition to inducing direct membrane protein oxidative modification, oxidative treatment, specifically triggers the phosphorylation of band 3 tyrosine residues. Our results suggest that selective Tyr-phosphorylation of oxidized band 3 by Syk may play a role in the recruitment of oxidized band 3 in large membrane aggregates that show high affinity to NAbs, leading to RBCs removal from circulation. The insufficient information about the PTMs occurring in a large majority of the red membrane proteins and the general lack of mass spectrometry data evidence the need of new comprehensive, proteomic approaches to improve the understanding of the red cell membrane physiology.