In mammals, it is present in two specific sites:[citation needed] The erythrocyte and kidney forms are different isoforms of the same protein.

[citation needed] Mutations of kidney AE1 cause distal (type 1) renal tubular acidosis, which is an inability to acidify the urine, even if the blood is too acidic.

[citation needed] Mutations of erythroid AE1 affecting the extracellular domains of the molecule may cause alterations in the individual's blood group, as band 3 determines the Diego antigen system (blood group).

[13] AE1 was discovered following SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) of erythrocyte cell membrane.

The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'.