Carboxypeptidase D (CPD) is a metallocarboxypeptidase enzyme with critical roles in peptide metabolism and protein processing. CPD localizes to sensory epithelium and nerve cells in the mouse cochlea, where its enzymatic activity is crucial for nitric oxide (NO) production through arginine processing 1. The enzyme's function is essential for hearing, as CPD deficiency leads to decreased levels of arginine, NO, and cGMP in patient-derived fibroblasts, triggering endoplasmic reticulum stress-mediated responses 1. Mechanistically, CPD processes arginine to support the NO signaling pathway, and silencing of Cpd in organotypic mouse cochlea cultures results in increased apoptosis 1. Disease relevance is significant, as three distinct missense variants in CPD affecting the catalytically active CP domain 2 have been identified in individuals with congenital deafness from unrelated families 1. Additionally, rare protein-altering CPD variants show enrichment in individuals with hearing loss 1. Clinically, CPD-related hearing loss represents a treatable condition, as Drosophila models of CPD deficiency with auditory defects can be partially rescued by supplementation with arginine or sildenafil, a cGMP enhancer, highlighting the NO signaling pathway as a promising therapeutic target 1.