PREPL (prolyl endopeptidase like) is a serine peptidase with both enzymatic and non-enzymatic cellular functions. As an enzyme, PREPL exhibits peptidase activity with unclear precise substrate specificity, though it does not cleave peptides after arginine or lysine residues 1. Beyond its hydrolytic function, PREPL plays critical roles in cellular trafficking by regulating trans-Golgi network morphology and sorting through modulation of AP-1 complex membrane binding 1. The protein may also contribute to synaptic vesicle exocytosis regulation 1. PREPL is clinically significant as mutations cause congenital myasthenic syndrome-22 (CMS22), a rare neuromuscular disorder characterized by impaired neuromuscular signal transmission 2. Interestingly, CMS22 can result from both loss-of-function variants and missense mutations that preserve enzymatic activity but disrupt protein-protein interactions, indicating that PREPL's non-catalytic functions are essential for normal neuromuscular function 1. PREPL has also been associated with hypotonia-cystinuria syndrome and primary ovarian insufficiency 3. Recent studies suggest PREPL may regulate mitochondrial function, with implications for cardiovascular diseases like atherosclerosis 4. The multifunctional nature of PREPL highlights its importance in both metabolic and structural cellular processes.