DPYSL2, also known as CRMP2, encodes a microtubule-stabilizing protein of great significance in neurogenesis. It is involved in multiple signaling pathways such as mTOR signaling, cytoskeletal dynamics, immune function, calcium signaling, and cholesterol biosynthesis. It has been associated with numerous psychiatric and neurodegenerative disorders, as well as cancer metastasis [1-3]. Genetic models, especially knockout models, are valuable in studying its functions.

In human iPSC-derived glutamatergic neurons, knockout of DPYSL2-B led to reduced dendrite length and disruptions in pathways relevant to psychiatric diseases, confirming its role in mTOR signaling and neurodevelopmental disorders [1]. In mesenchymal-like breast cancer cells, DPYSL2 knockout profoundly inhibited cell migration, invasion, stemness features, tumor growth rate, and metastasis, revealing its role in the interaction with JAK1 to mediate cancer cell migration [2]. In zebrafish, dpysl2 knockout mutants exhibited abnormalities in the migration of facial branchiomotor neurons, indicating its requirement for proper neuronal migration during development [3].

In summary, DPYSL2 is crucial for neurogenesis, neuronal migration, and plays roles in various disease-related processes. The gene knockout models in different organisms have significantly contributed to understanding its functions in psychiatric and neurodegenerative disorders, as well as in cancer metastasis.