The Multifaceted Role of AASDH: From Metabolic Regulation to Cancer and Cardiomyopathies.

The enzyme 2-aminoadipic-6-semialdehyde dehydrogenase (AASDH) plays a crucial role in metabolic pathways and has emerged as a significant player in multiple pathological conditions, including cancer and cardiomyopathies. AASDH has been implicated in colorectal cancer (CRC), particularly in microsatellite instability (MSI)-high tumors, in which genetic alterations may contribute to chemotherapy resistance and tumor progression. In addition to CRC, dysregulation of AASDH has been observed in hepatocellular carcinoma (HCC) and lung adenocarcinoma (LUAD), where it influences lipid metabolism and oncogenic pathways. Additionally, emerging evidence suggests a strong link between AASDH and cardiomyopathies, highlighting its potential as a biomarker of ischemic cardiomyopathy-induced heart failure. At the molecular level, AASDH functions in ATP binding and acid-thiol ligase activity, and plays a pivotal role in stress responses, lysine metabolism, and oxidative stress protection. Its association with metabolic reprogramming and the tumor microenvironment suggests that targeting AASDH could enhance current therapeutic strategies for cancer and cardiovascular diseases. This review comprehensively explores the diverse roles of AASDH, emphasizing its potential as a prognostic biomarker and therapeutic target for multiple diseases. A deeper understanding of AASDH may pave the way for novel treatment strategies that integrate metabolic modulation with conventional therapies and improve clinical outcomes in both oncology and cardiology.