ABCF1 is an ATP-binding cassette protein lacking a transmembrane domain that functions as a multifaceted regulator of immunity and gene expression rather than a transporter 1. Its primary canonical function involves mRNA translation initiation via Cap- and IRES-mediated mechanisms, though recent evidence reveals substantial noncanonical roles 1. Mechanistically, ABCF1 operates through diverse pathways. It acts as a cytosolic dsDNA sensor activating type I interferon responses and CXCL10 production in airway epithelial cells 2. Against hepatitis B virus, ABCF1 recognizes cccDNA and forms phase-separated condensates that inhibit viral transcription while activating interferon signaling 3. Additionally, ABCF1 binds 2'-5' oligoadenylates, nucleotide second messengers in innate immunity, though functional consequences remain unclear 4. In glioblastoma, ABCF1 enhances cell proliferation and invasion by upregulating the CXCL12/CXCR4 axis and activating PI3K/AKT signaling 5. Regarding disease relevance, ABCF1-K430 lactylation promotes hepatocellular carcinoma progression through nuclear translocation and transcriptional activation of the KDM3A-H3K9me2-HIF1A axis 6, establishing a lactate-ABCF1-HIF1A feedback loop 7. However, ABCF1's role in TNF-α and Poly(I:C)-induced inflammatory responses appears independent of NF-κB activation in airway epithelial cells 8, highlighting context-dependent functions. These findings position ABCF1 as a potential therapeutic target across cancers and infectious diseases.