SH3PXD2A encodes Tks5, a scaffold protein that plays critical roles in cellular invasion and extracellular matrix remodeling through invadosome and podosome formation 1. The protein contains SH3 and PX domains and acts as an organizer for NADPH oxidase-dependent reactive oxygen species generation 1. The gene produces multiple isoforms, including Tks5β which lacks the PX domain and has distinct regulatory properties 1. In development, SH3PXD2A is essential for mammalian embryogenesis, as homozygous disruption results in neonatal death and cleft palate formation 1. The gene has significant disease relevance across multiple conditions. Genetic variants in SH3PXD2A are associated with stroke risk, particularly lacunar stroke, where it contributes to vascular extracellular matrix disruption 23. The gene is also implicated in intracerebral hemorrhage susceptibility 4 and cerebral white matter hyperintensities through DNA methylation mechanisms 5. In oncology, SH3PXD2A-HTRA1 fusion genes occur in 12.7% of intracranial schwannomas, particularly trigeminal schwannomas, and are associated with more aggressive tumor behavior and higher recurrence rates 6. Additionally, mutations in SH3PXD2A contribute to rosacea pathogenesis through neurogenic inflammation pathways involving vasoactive neuropeptide production 7. These findings establish SH3PXD2A as a key regulator of cellular invasion, vascular integrity, and tumor progression.