GDF15 and familial pancreatic carcinoma: The GFRAL-GDF15 complex binds to the tyrosine kinase co-receptor RET, which phosphorylates to initiate a signaling cascade and subsequently activates intracellular signaling pathways such as AKT, ERK1/2, and phospholipase C γ(PLC γ), but not the SMAD pathway.[41,42] A recent study found that pancreatic cancer tissues have significantly higher levels of GFRAL expression compared to healthy pancreatic tissues.