MEP1B encodes meprin β, a membrane-bound metalloprotease that regulates tissue homeostasis through proteolytic cleavage of cell-adhesion molecules and extracellular matrix components 1. The enzyme exhibits substrate specificity for acidic amino acids and cleaves diverse targets including inflammatory cytokines (IL1B, IL18), growth factors (FGF19, VGFA), structural proteins (E-cadherin, collagen), and APP to generate amyloid-β 2. MEP1B localizes to chromosome 18.2-q12.3 and undergoes alternative splicing generating tissue-specific isoforms 3. Clinically, MEP1B dysfunction associates with barrier dysfunction diseases. Meprin β regulates blood-brain barrier integrity by cleaving tight junction proteins (claudin-5, occludin); Mep1b knockout mice show increased tight junction protein expression and reduced BBB permeability, whereas overexpression decreases barrier integrity 1. MEP1B gene polymorphisms correlate with diabetic nephropathy susceptibility in Pima Indians, with multiple SNPs showing within-family association; notably, SNP18 causes a proline-to-leucine change in the cytoplasmic tail 4. Recent proteogenomic studies identified MEP1B as causally associated with serum HDL cholesterol levels 5. These findings establish MEP1B as a critical regulator of epithelial barrier function with relevance to neurodegenerative and metabolic diseases.