Pancreatitis is thought to be a disease of autodigestion triggered by premature and intracellular activation of digestive proteases.¹ We and others have shown that lysosomal cathepsin B can activate trypsinogen intracellularly² and that a large proportion of pancreatic cathepsin B is physiologically sorted into the secretory compartment.³ Further support for a role of cathepsin B in pancreatitis came from a recent study published by Mahurkar and coworkers in Gut⁴ in which the authors reported that a leucine to valine mutation at position 26 of cathepsin B (L26V) is associated with tropical calcifying pancreatitis (odds ratio ∼2.2) in patients from southern India. Tropical calcifying pancreatitis is also associated (in up to 50% of cases) with mutations in the SPINK1 gene⁵—with N34S being the most common mutation. In the study by Mahurkar et al the cathepsin B L26V …