Taken together, to the best of our knowledge, this is the first evidence demonstrating cytosolic Neu2 on the membrane which plays as an upstream important molecule for establishing a cross-talk between Neu2, activation of Fas, induction of extrinsic pathway and inhibition of PI3K pathway to induce apoptosis in drug-resistant human pancreatic cancer cells. Here, NEU2 is linked to familial pancreatic carcinoma.