Tubulin normally undergoes a cycle of detyrosination/tyrosination on the carboxy terminus of its alpha-subunit and this results in subpopulations of tyrosinated tubulin and detyrosinated tubulin. Brain tubulin preparations also contain a third major tubulin subpopulation which is non-tyrosinatable. This review describes the purification and the structural characterization of non-tyrosinatable tubulin. This tubulin variant lacks a carboxyterminal glutamyl-tyrosine group on its alpha-subunit (delta2-tubulin). Delta2-tubulin is generated from detyrosinated tubulin through an irreversible reaction. Delta2-tubulin accumulates in neurons and in stable microtubule assemblies. It also accumulates in some tumor cells due to the frequent loss of tubulin tyrosine ligase in such cells. Delta2-tubulin may be a useful marker of malignancy in human tumors.