AOPEP encodes aminopeptidase O, a zinc-dependent proteolytic processing enzyme that catalyzes hydrolysis of amino acid residues from the N-terminus of peptide and protein substrates 1. The protein is preferentially expressed in glial cells and is potentially linked to endosomal-lysosomal pathways and synaptogenesis 12. AOPEP is associated with autosomal recessive dystonia (Zech-Boesch syndrome), with 74% of disease-associated alleles being protein-truncating variants including stop-gain, frameshift, and splice-site mutations 1. Affected individuals present with childhood to adult-onset dystonia, frequently generalizing across body regions (60% of cases), and variable expressivity suggesting age-dependent penetrance 13. Biallelic loss-of-function variants cause progressive dystonia with prominent limb involvement, occasionally accompanied by parkinsonism 24. Functionally, AOPEP variants show convergent neural dynamics in the globus pallidus characterized by altered firing regularity and bursting patterns comparable to other dystonia genes, despite lacking shared molecular pathways 5. Additionally, AOPEP promoter SNPs regulate alternative splicing affecting miR-27b-3p expression, relevant to kidney fibrosis in diabetic nephropathy 6. AOPEP genetic variants also show evidence of positive selection in polycystic ovary syndrome susceptibility 7.