Sorcin: (i) is an essential protein, one of the most expressed calcium-binding proteins in the human brain; (ii) is overexpressed in models of neurodegenerative diseases; (iii) regulates calcium homeostasis by regulating calcium channels (RyR and SERCA in the ER), increases ER Ca2+ load, participates in preventing ER stress and the unfolded protein response; iv) interacts in a calcium-dependent fashion with αSyn, presenilin2 (PS2) and other proteins, and regulates PS258,59; for these reasons, Sorcin may represent a useful marker and an important player in the mechanisms of neurodegeneration. Here, PSEN2 is linked to neurodegenerative disease.