The invention provides methods and compositions for identifying agents that modulates 138-kDa C2 domain-containing phosphoprotein (CDP138) activity or phosphorylation levels both in vivo and in vitro. Also provided are methods and compositions to prolong the survival of neuronal cells, to ameliorate or prevent a condition associated with release of insulin from insulin producing cells and insulin-stimulated glucose metabolism, to inhibiting proliferation of a cancer cell and to inducing cell cycle arrest of a cancer cell.