Abstract: Methods to determine the susceptibility of a subject to erythrocyte diseases are provided. The methods comprise determining the miRNA compositions of erythrocytes from the subject. The present invention has discovered that erythrocytes comprise microRNA (miRNA) populations and the populations can be profiled or analyzed and used to determine the susceptibility for disease. The miRNA compositions can also be used to determine the severity of erythrocyte disease, and the features and clinical phenotypes of the erythrocyte disorders. Also provided are pharmaceutical compositions comprising erythrocyte miRNAs and methods for the treatment of a subject with an erythrocyte disease. In other embodiments of the invention, the miRNAs can be used to increase the life-span of erythrocytes through the introduction of an erythrocyte miRNA.