Sushi repeat-containing protein X-linked 2 (SRPX2)

Sushi repeat-containing protein X-linked 2 (SRPX2) is a secreted extracellular matrix protein characterized by three sushi (CCP) domains and one HYR domain, encoded on the X chromosome. It serves as a ligand for the urokinase plasminogen activator receptor (uPAR), is essential for synapse formation in the brain, and supports neuronal, angiogenic, and migratory processes. SRPX2 is widely expressed, notably in the brain, where it plays roles in language development, synaptic plasticity, and hypothalamo-pituitary signaling. Pathogenic mutations are linked to neurodevelopmental disorders, including speech dyspraxia and epilepsy; overexpression is strongly associated with various cancers, promoting malignancy via major signaling pathways (TGF-β, PI3K/Akt/mTOR, Wnt/β-catenin, Hippo/YAP, FAK/SRC/ERK). SRPX2 is increasingly recognized as a prognostic biomarker and potential therapeutic target in oncology and neurology, though no approved drugs directly target it as of the current literature[1][2][3][4][5].

Other names

SRPX2SRPULSushi-repeat protein upregulated in leukemiaBPPCBPSPMGXRESDXSushi repeat containing protein, X-linked 2Sushi-repeat-containing protein SRPX2

Experimental inhibition (siRNA, anti-sense) suppresses SRPX2 function, resulting in reduced tumor cell adhesion, migration, invasion, metastasis, and impacts on EMT-pathways (such as PI3K/Akt/mTOR, FAK, Wnt/β-catenin, Hippo/YAP, MAPK)[1][2]. Knockdown of SRPX2 can inhibit oncogenic signaling, tumor progression, and metastasis experimentally[1][2].