SRPX2, or Sushi-repeat-containing protein, X-linked, 2 (OMIM*300642), is a gene located on Xq22.1 that encodes a secreted protein highly expressed in cerebral cortex neurons. It is involved in multiple biological processes such as neurodevelopment, learning, and synapse formation. It has been found to interact with FOXP2, a gene related to speech and language disorder, and FoxP2 controls SRPX2's expression timing and level [1].

In mice, SRPX2 is needed for vocalization and synapse formation. Silencing SRPX2 or injecting specific variants in mouse models leads to alterations in neuronal migration in the cerebral cortex and epilepsy, indicating its crucial role in neurodevelopment [1].

In cancer-related studies, SRPX2 promotes the proliferation and migration of papillary thyroid cancer cells in vitro and in vivo, potentially through activating the PI3K/AKT or FAK pathways [2,3]. In pancreatic cancer, it is associated with chemoresistance by activating the PI3K/AKT axis, and its combination with RAB31 can be an important prognostic marker [4,5]. In esophageal squamous cell carcinoma, knockdown of SRPX2 suppresses cell proliferation, metastasis, and promotes chemosensitivity through the inactivation of the Wnt/β-catenin signaling pathway [6]. In non-small cell lung cancer, it promotes cell proliferation and invasion via activating the FAK/SRC/ERK pathway [7]. In colorectal cancer, circSEC24B activates autophagy and induces chemoresistance by promoting the deubiquitination of SRPX2 [8].

In conclusion, SRPX2 is essential for neurodevelopment, especially in aspects like synapse formation and neuronal migration. In the context of cancer, it promotes tumor-related processes such as cell proliferation, migration, and chemoresistance across multiple cancer types. Mouse models, especially those with SRPX2 knockdown or variant injection, have been instrumental in revealing its functions in neurodevelopmental disorders and cancer-related disease conditions.