Erythrocyte membrane protein band 4.2 is an ATP-binding protein which may regulate the association of protein 3 with ankyrin. It probably has a role in erythrocyte shape and mechanical property regulation. Mutations in the EPB42 gene are associated with recessive spherocytic elliptocytosis and recessively transmitted hereditary hemolytic anemia.

The deduced 691-amino acid band 4.2 protein has homology with 2 closely related calcium-dependent crosslinking proteins, guinea pig liver transglutaminase and the alpha subunit of human coagulation factor XIII (F13A1). Within the 5 contiguous consensus residues of the transglutaminase active site, band 4.2 has an amino acid substitution which leads to loss of transglutaminase activity.