LYRM2 is a mitochondrial protein primarily involved in complex I assembly and function. It directly integrates the N-module into mitochondrial respiratory chain complex I 1, and knockout studies demonstrate that LYRM2 loss impairs NADH-dehydrogenase module assembly, leading to respiratory defects 1. The protein interacts with the mitochondrial acyl-carrier protein NDUFAB1 as part of the LYRM family's essential role in mitochondrial metabolism 1. In cancer contexts, LYRM2 exhibits oncogenic properties distinct from its metabolic role. In colorectal cancer, LYRM2 is upregulated and directly increases complex I activity to enhance oxidative phosphorylation, promoting tumor growth through an Akt-S58phos-LYRM2-Complex I axis 2. In hepatocellular carcinoma, LYRM2 promotes growth and metastasis via an alternative mechanism—interacting with HIF-1α to enhance its stability, thereby promoting glycolysis while inhibiting mitochondrial respiration 3. Beyond cancer, LYRM2 has been identified as a vBMD-associated gene in bone mineral density studies 4 and as a diagnostic biomarker for major depressive disorder as part of a seven-gene mitochondrial signature 5. Environmental factors also influence LYRM2; arsenic exposure associates with significant DNA methylation changes within the LYRM2 gene in placental tissue 6.