SFXN3 (sideroflexin 3) is a mitochondrial inner membrane protein that functions primarily as a serine transporter essential for one-carbon metabolism 1. SFXN3 facilitates the transport of serine into mitochondria, where it is converted to glycine and formate, providing one-carbon units required for nucleotide synthesis and other critical metabolic processes 1. The protein works cooperatively with SFXN1, as cells lacking both transporters show severe metabolic defects including glycine auxotrophy 1. Beyond its metabolic role, SFXN3 participates in mitochondrial iron homeostasis through interaction with the PCBP2-TOM20-SFXN3 axis, contributing to iron entry into mitochondria distinct from the MFRN1 pathway 2. SFXN3 also regulates synaptic morphology in an α-synuclein-dependent manner, suggesting involvement in neuronal function 3. Clinically, SFXN3 has emerged as a biomarker with elevated serum autoantibodies detected in oral squamous cell carcinoma patients with 77% sensitivity and 89% specificity 4. The protein is also associated with poor prognosis in head and neck squamous cell carcinoma and cervical cancer, where its expression correlates with immunosuppressive environments and chemoresistance 56. These findings establish SFXN3 as a multifunctional mitochondrial protein with roles in metabolism, iron homeostasis, neuronal function, and cancer progression.