SLC25A45 (solute carrier family 25 member 45) is a mitochondrial inner membrane transporter recently identified as essential for the import of methylated amino acids. Dias et al. (2025, Molecular Cell) demonstrated that SLC25A45 specifically mediates the mitochondrial uptake of dimethylarginine and trimethyllysine, but not their unmethylated counterparts. This selective transport enables mitochondria to metabolize trimethyllysine for de novo carnitine biosynthesis, linking SLC25A45 activity to fatty acid oxidation and methylated amino acid homeostasis. A naturally occurring human variant, R285C, enhances SLC25A45 stability by disrupting m-AAA protease-dependent degradation and is associated with altered plasma levels of methylated amino acids and deoxycarnitine. Functionally, SLC25A45 defines a key metabolic node coordinating methylated amino acid turnover, carnitine synthesis, and mitochondrial signaling, implicating it in cardiovascular, renal, and metabolic pathophysiology. (PMID: 41075794)