3‐Hydroxyacyl‐CoA dehydratase 2 (HACD2) promotes pancreatic cancer progression by binding to PRKN and promoting dissociating PKM2 from PRKN in a dehydratase‐independent manner, resulting in a decrease in PKM2 ubiquitination and an increase in PKM2 dimerization, followed by the promotion of c‐Myc expression and tumor growth. Here, PKM is linked to familial pancreatic carcinoma.