APEH (acylaminoacyl-peptide hydrolase) is an exopeptidase that catalyzes the hydrolysis of N-terminal peptide bonds in N-acetylated and N-formylated peptides, preferentially cleaving N-acetylated amino acids like Ac-Ala, Ac-Met, and Ac-Ser 1. The enzyme also displays endopeptidase activity toward oxidized and glycated proteins, functioning sequentially with ACY1 in N-acylated peptide degradation 1. APEH protects cells by degrading protein carbonyls, oxidative modifications that trigger endoplasmic reticulum stress and the unfolded protein response 1. Beyond proteolysis, APEH localizes to nuclear DNA damage sites via interaction with XRCC1, facilitating single-strand break repair and cell survival following oxidative stress 2. APEH activity is inhibited by lipid metabolites and peroxidation products, potentially serving as a biomarker for oxidative stress in diseases 3. Clinically, APEH represents a druggable target across multiple disease contexts: genome-wide association studies identify APEH as a pleiotropic gene affecting type 2 diabetes, muscle mass, and frailty 4; it is implicated in acute kidney injury pathogenesis 5; and the HNF4A/APEH axis regulates protein carbonylation and unfolded protein response signaling in diabetic kidney disease 1. APEH genetic variants (rs4855883) correlate with radiotherapy-induced oral mucositis severity in head and neck cancer patients 6.