DMAC2 (distal membrane arm assembly component 2) is a mitochondrial protein essential for complex I biogenesis. It is specifically required for assembly of the distal region of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I), a critical component of the electron transport chain. Beyond its structural role in oxidative phosphorylation, DMAC2 may participate in protein quality control through involvement in SCF ubiquitin ligase complex-mediated proteasomal degradation pathways. Recent genetic studies have identified DMAC2 as a disease-relevant locus in cardiovascular pathology. Specifically, DMAC2 alternative splicing patterns, which are regulated by both genetic variants and inflammatory signals (interleukin-1β), colocalize with genome-wide association study signals for coronary artery disease risk 1. This splicing-mediated genetic mechanism suggests that variation in DMAC2 isoform expression, particularly in endothelial cells responding to inflammatory stimuli, may contribute to individual cardiovascular disease susceptibility. The identification of DMAC2 as a genetically regulated splicing target provides a plausible molecular explanation linking mitochondrial complex I assembly function to atherosclerotic disease pathogenesis, highlighting the importance of energy metabolism in endothelial dysfunction.