PNLIP encodes pancreatic triglyceride lipase, a 56-kDa enzyme essential for dietary fat digestion in the small intestine 1. The enzyme preferentially hydrolyzes triglyceride esters at positions 1 and 3, producing 2-monoacylglycerol and free fatty acids, with substantially higher activity against emulsified substrates [UniProt]. Beyond its canonical digestive role, PNLIP mediates systemic lipotoxicity during acute pancreatitis: pancreatic lipase translocates into visceral adipose tissue, hydrolyzes adipocyte triglycerides, and generates excess nonesterified fatty acids that independently cause organ failure 2. PNLIP dysfunction is associated with chr10 pancreatitis through multiple mechanisms. Protease-sensitive variants (P245A, I265R, F300L, S304F, F314L) exhibit reduced stability upon exposure to pancreatic proteases and segregate with early-onset pancreatitis in families 34. Alternatively, misfolding variants such as T221M cause proteotoxicity: mutant protein aggregates in the endoplasmic reticulum, triggering ER stress and maladaptive unfolded protein responses that lead to acinar cell death and progressive pancreatic atrophy 5. Congenital pancreatic lipase deficiency results from PNLIP variants with impaired secretion 6. PNLIP expression is regulated by undercarboxylated osteocalcin through cAMP/PKA/ATF4 signaling 7, suggesting integration with systemic energy metabolism.