Snx14, or sorting nexin 14, is a member of the sorting junction protein family. It has diverse functions including regulating lipid homeostasis, autophagy, and receptor signaling [1,2,4]. It is associated with pathways such as the PI3K/AKT/mTOR signaling cascade and is involved in maintaining the balance of lipid saturation in cell membranes [1,5]. Genetic models, especially mouse models, have been crucial in understanding its functions.

In mouse models, Snx14 deficiency has been linked to various phenotypes. Snx14 -deficient mice show severe motor deficits and Purkinje cell degeneration due to disrupted microtubule organization and mitochondrial transport in axons, leading to cerebellar ataxia [3]. In breast cancer, knockdown of Snx14 in an MCF7 breast cancer tumor-bearing mouse model inhibited tumorigenicity and tumor cell growth, as Snx14 normally promotes breast cancer cell proliferation and inhibits autophagy via the PI3K/AKT/mTOR pathway [1]. SNX14KO cells have defective lipid metabolism, with compromised ER integrity and hypersensitivity to saturated-fatty-acid-mediated lipotoxic cell death [5].

In conclusion, Snx14 plays essential roles in lipid metabolism, autophagy, and neuronal function. Mouse models with Snx14 deficiency, such as KO or CKO models, have been instrumental in revealing its roles in cerebellar neurodegeneration and ataxia, as well as in breast cancer development. Understanding Snx14 functions provides insights into the mechanisms of these diseases and potential therapeutic targets.