TAMM41 is a mitochondrial inner membrane protein that catalyzes the conversion of phosphatidic acid to CDP-diacylglycerol, a critical intermediate in cardiolipin, phosphatidylglycerol, and phosphatidylinositol biosynthesis 1. The protein maintains mitochondrial function and regulates PINK1-PARK2-dependent mitophagy 2. Clinically, TAMM41 dysfunction is associated with multiple disease states. Reduced TAMM41 expression correlates with Alzheimer's disease risk, with gene-based association studies showing significant evidence for mitochondrial involvement in neurodegeneration 3. TAMM41 variants cause combined oxidative phosphorylation deficiency 56 and mitochondrial myopathy, presenting with neonatal hypotonia, developmental delay, and progressive weakness with decreased respiratory enzyme staining 4. In cardiac development, TAMM41 deficiency leads to congenital heart valve abnormalities through impaired mitophagy, with heterozygous pathogenic variants identified in atrioventricular septal defect patients 2. Recent mechanistic studies reveal TAMM41's role in antidepressant responses: ketamine-induced antidepressant effects require TAMM41-mediated transfer of sigma-1 receptor from astrocytes to neurons via cardiolipin-exosome pathway 5, and genetic TAMM41 overexpression produces antidepressant-like effects through pacsin1 regulation 1. TAMM41 methylation changes are associated with diabetic kidney disease progression 6.