Fgf13, a non-canonical, non-secreted fibroblast growth factor, is involved in multiple biological processes. It interacts with microtubules and is associated with pathways related to calcium signaling, ion channel regulation, and immune-related functions. Genetic models, such as KO and CKO mouse models, have been crucial for studying its functions [1,2,6].

In heart failure models, Fgf13 deficiency alleviates cardiac dysfunction by improving abnormal calcium signaling through inhibiting increased microtubule stability [1]. In dorsal root ganglion neurons, conditional knockout of Fgf13 impairs scratching behaviors in acute and chronic itch models, as it selectively regulates TRPV1 function via microtubule-stabilizing effect [2]. In AML patients, low Fgf13 expression is related to prognosis, and overexpression in xenograft models inhibits AML cell growth [3]. In diabetic nephropathy, endothelial-specific deletion of Fgf13 alleviates damage by improving mitochondrial homeostasis [4]. Obesity-induced Fgf13 in adipose tissue impairs energy and glucose homeostasis [5]. Interneuron-targeted deletion of Fgf13 leads to seizures and affects K⁺ channel currents [6]. Stable Fgf13 depletion in triple-negative breast cancer cells restricts metastasis [7]. Loss of Fgf13 in mouse DRG neurons impairs histamine-induced scratching behavior [8]. Fgf13 up-regulation in cardiac hypertrophy has a deteriorating role, and its deficiency inhibits NF-κB activation [9]. Cardiac Fgf13 knockdown alleviates fibrosis by modulating microtubule stabilization and ROCK signaling pathway [10].

In conclusion, Fgf13 plays essential roles in various biological processes including calcium homeostasis, itch sensation, cancer development, metabolic regulation, and neuronal excitability. Gene knockout and conditional knockout mouse models have significantly contributed to understanding its functions in heart failure, leukemia, diabetic nephropathy, metabolic diseases, epilepsy, and breast cancer, providing potential therapeutic targets for these diseases.