Sfxn3, also known as citrate transporter protein-like protein (CTPL) in rats, is a mitochondrial protein. It functions as a serine transporter involved in one-carbon metabolism, which is crucial for synthesizing metabolites like nucleotides [2]. Sfxn3 is also associated with iron entry into mitochondria through the PCBP2-TOM20-SFXN3 axis [5]. It has been implicated in various biological processes, and its tissue-specific expression, especially neuronal enrichment, suggests specialized functions [3,7].

In acute myeloid leukemia (AML), especially non-M3 AML, high SFXN3 expression is associated with poor clinical outcomes, frequent blast cells, and promotes DNA methylation at transcription start sites. Non-M3 AML patients with high SFXN3 levels have a higher complete remission (CR) ratio when receiving hypomethylating therapy [1]. In addition, knockdown of SFXN3 in AML cells enhances apoptosis and reduces proliferation, and is related to the immunosuppressive state of AML [4].

In the nervous system, Sfxn3-KO mice show disrupted proteins and pathways associated with neurodegeneration and cell death, while overexpression of its orthologues in Drosophila models of Parkinson's disease reduces dopaminergic neuron loss, indicating its anti-neurodegeneration role [3]. In mice, Sfxn3 mutations lead to progressive outer retinal degeneration, with disrupted synapses in the outer plexiform layer, suggesting its role in retinal function [6].

In conclusion, Sfxn3 plays essential roles in multiple biological processes and disease conditions. Its functions in one-carbon metabolism, iron entry into mitochondria, and regulation of cell survival and differentiation are well-demonstrated. Studies using gene knockout models in mice have been crucial in revealing its roles in AML, neurodegeneration, and retinal function, providing potential biomarkers and therapeutic targets for these diseases.