Haptoglobin-2 precursor (pre-haptoglobin-2), commonly referred to as Zonulin (Zonulin (no universal abbreviation, sometimes "pre-HP2"))

Zonulin is a protein identified as the precursor to haptoglobin-2 (pre-HP2) and recognized as the only physiological modulator of intercellular tight junctions described so far, responsible for reversible regulation of paracellular permeability in epithelial and endothelial cells. Zonulin is upregulated in response to luminal triggers (e.g., gliadin, bacteria), participates in innate immune defense, and is implicated in pathogenesis of various autoimmune, inflammatory, and neurological disorders through its role in increased tissue permeability. Therapeutic modulation of the zonulin pathway with antagonists like larazotide acetate is being investigated to restore barrier integrity and potentially limit disease progression in conditions characterized by leaky barriers. Technical challenges exist in measurement and specificity, since zonulin is a family of related proteins, and the exact physiological role is still being elucidated.

Other names

Zonulinpre-haptoglobin-2zonulin family peptides (ZFP)zonulin-related proteins (ZRP)zonula occludens toxin homolog

Antagonists (e.g., larazotide acetate, FZI/0) bind zonulin receptors or inhibit zonulin activity, restoring tight junction integrity and reducing pathological intestinal permeability