Fbp2, also called muscle FBP, is a multifunctional protein and a glyconeogenesis-regulating enzyme [3]. It plays a role in various biological processes, such as the regulation of mitochondrial motility, microtubule stability [1], memory formation [3], and is involved in the reverse Warburg effect in cancer cells [7].

In HL-1 cardiomyocytes, reducing the FBP2 dimer-tetramer ratio (imitating AMP and NAD+ action) leads to increased Tau phosphorylation, augmented FBP2-Tau and FBP2-MAP1B interactions, tubulin network disturbance, reduced mitochondrial trafficking speed, and increased mitophagy, highlighting its role in cardiac remodeling and related diseases [1].

In oral squamous cell carcinoma (OSCC), FBP2 is downregulated. Overexpression of FBP2 suppresses OSCC cell viability, proliferation, migration, and glycolysis, while knockdown promotes these processes, and it acts through down-regulation of c-Myc [6]. Also, TRIM32, an E3 ubiquitin ligase, promotes OSCC progression by enhancing FBP2 ubiquitination and degradation [4].

In gastric cancer, hsa_circ_0026344 inhibits cell proliferation via the miR-1290/FBP2 axis [2]. A heterozygous variant in FBP2 is associated with a novel remitting leukodystrophy, disturbing cerebral energy metabolism [5].

In conclusion, Fbp2 is crucial for multiple biological functions including mitochondrial and microtubule regulation, and has significant implications in various diseases such as cardiac-related disorders, different types of cancers, and a novel leukodystrophy. Studies on Fbp2, especially through loss-of-function models, help to understand its role in these disease conditions, providing potential targets for treatment [1,2,4,5,6].