A new isoform of manganese superoxide dismutase (MnSOD) and polynucleotides encoding it have been identified. This isoform, MnSOD E3(-), is a splice variant lacking exon 3 of the full length MnSOD. The polypeptide can be expressed using appropriate host cells. Modulation of either the expression of the polynucleotides of the activity of the polypeptide is also described. Furthermore, diagnostic and therapeutic methods have been developed as a consequence of the isolation of the polynucleotides and polypeptides.