PRND

PRND encodes the prion-like protein doppel (DPL), also termed PRND-derived protein or Prnd. Structurally homologous to cellular prion protein (PrPC) but lacking its neuroprotective properties, doppel is a GPI-anchored glycoprotein predominantly expressed in testicular germ cells and cerebellar neurons. It interacts with cellular membranes through its N-terminal hydrophobic domain, modulating G-protein coupled receptor signaling and influencing sperm-egg fusion during fertilization. Doppel activates pro-apoptotic pathways via interaction with Bax, contributing to mitochondrial membrane permeabilization. Aberrant expression correlates with prion disease progression, particularly in PrP-null models of scrapie and Creutzfeldt-Jakob disease. Elevated doppel levels are implicated in male infertility and neurodegenerative disorders. While no clinical inhibitors exist, experimental approaches targeting doppel-PrP interactions using monoclonal antibodies (e.g., 8B4) and siRNA-mediated silencing have shown efficacy in reducing neurotoxicity in murine models. Its role in zinc homeostasis and synaptic plasticity remains under investigation.