Carboxymethylenebutenolidase homolog

Carboxymethylenebutenolidase homolog (CMBL) is a cysteine hydrolase whose endogenous physiological substrates remain unknown (UniProt: Q96DG6). The protein catalyzes hydrolytic activation of ester-based prodrugs by cleaving dioxolone rings, including the angiotensin receptor blockers Olmesartan medoxomil and Azilsartan medoxomil, as well as beta-lactam antibiotics such as Faropenem medoxomil and Lenampicillin. Its expression pattern and subcellular localization across tissues have not been extensively characterized in the UniProt knowledge base.

In Alzheimer's Disease, CMBL is elevated in post-mortem brain tissue from AD patients compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics analysis across four subcellular fractions (P2, P3, S2, S3) using TMT-labeled, data-dependent acquisition mass spectrometry detected the protein with a mean log2 fold-change of 1.09, indicating consistent upregulation across fractions. The functional relevance of increased CMBL expression in AD pathophysiology is not established and warrants further investigation.