Pancreatitis-associated protein (PAP)

Pancreatitis-associated protein (PAP) is a 16 kDa secretory protein belonging to group VII of the C-type lectin family, originally discovered in the pancreatic juice following acute pancreatitis in rats. There are three main paralogs in humans (PAP I, II, and III), with expression induced primarily during acute inflammation, especially in the pancreas and also the intestine. PAP acts as part of the acute-phase response, displaying anti-inflammatory, anti-apoptotic, mitogenic, and antibacterial activities, such as aggregating bacteria to protect against infection in pancreatitis. It is also implicated as a marker and possible mediator in inflammatory diseases (particularly pancreatitis) and in the pathogenesis and progression of certain cancers (notably pancreatic ductal adenocarcinoma). PAP can induce expression of anti-inflammatory factors via the JAK/STAT3/SOCS3 pathway and, under some circumstances, may contribute to distant organ inflammation, such as lung injury during acute pancreatic episodes through TNFα induction in the liver. PAP is not generally considered a classic therapeutic target (such as a receptor or enzyme), but is a tissue injury marker and potential biomarker for disease diagnosis and severity.

Other names

Peptide 23HIP (Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein)Pancreatitis-associated protein I (PAP I)Pancreatitis-associated protein II (PAP II)Pancreatitis-associated protein III (PAP III)Regenerating islet-derived protein III (REG III)Reg IIIβReg IIIγ

For PAP itself: Acts as an endogenous anti-bacterial agent by aggregating bacteria; anti-inflammatory action via JAK/STAT3/SOCS3 pathway activation. For relevant drugs (e.g., chloroquine), their mechanism of action, such as inhibition of autophagy, is noted in the context of other related proteins like VMP1, not PAP itself.