RNPEP (arginyl aminopeptidase) is a zinc-dependent metalloexopeptidase that selectively removes arginine and/or lysine residues from the N-terminus of peptide substrates 1. The protein contains the canonical M1 metallopeptidase signature sequence and is ubiquitously expressed across human tissues with variable expression levels 1. RNPEP participates in neuropeptide processing alongside other proteases, displaying relatively even expression throughout human brain regions including the hypothalamus 2. In disease contexts, RNPEP serves as a potential biomarker for small cell lung cancer (SCLC), being identified as a marker for NEUROD1-high SCLC subtypes in bronchoalveolar lavage fluid 3. Most notably, tumor-derived exosomal RNPEP promotes hepatocellular carcinoma lung metastasis by activating cancer-associated fibroblasts through NF-κB signaling, with elevated RNPEP levels detected in plasma of HCC patients 4. RNPEP has been identified as differentially expressed in esophageal carcinoma cells 5 and is part of the local bone marrow renin-angiotensin system involved in hematopoietic regulation 6. Additionally, reduced RNPEP abundance in sperm is associated with obesity-related male subfertility 7, and genetic variation at the RNPEP locus affects serum butyrylcholinesterase activity independent of metabolic factors 8.