SFXN1 is a mitochondrial inner membrane serine transporter that functions as a critical component of one-carbon metabolism 1. It mediates serine import into mitochondria, where serine is converted to glycine and formate; these products exit to the cytosol to generate charged folates serving as one-carbon donors 1. SFXN1 may also transport alanine and cysteine 1. The transporter functions within a regulatory complex; SERAC1 at the outer mitochondrial membrane facilitates SFXN1-mediated serine transport 2, while the microprotein SMIM26 coordinates serine import with complex I biogenesis through mitoribosome interactions 3. One-carbon metabolism dysfunction from SFXN1 loss impairs nucleotide synthesis and mitochondrial DNA maintenance 2. Clinically, SFXN1 is frequently upregulated in lung adenocarcinoma and bladder cancer, correlating with poor prognosis and enhanced metastatic potential 4 5. However, SFXN1 exhibits context-dependent roles: it promotes cancer progression in lung adenocarcinoma and triple-negative breast cancer through mechanisms beyond classical one-carbon metabolism 6 7, yet loss of SFXN1 in non-viral hepatocellular carcinoma mitigates lipotoxicity and associates with improved survival 8, suggesting tissue-specific or metabolic-context-dependent functions warranting further investigation.