BRK1 (BRICK1) is a microprotein subunit of the WAVE actin regulatory complex that orchestrates actin polymerization and cytoskeletal dynamics 1. As a component of the pentameric WAVE complex alongside CYFIP, NCKAP, and ABI proteins, BRK1 activates the Arp2/3 complex to promote lamellipodia and invadopodia formation 2. BRK1 exists as a homotrimeric precursor that becomes incorporated into functional WAVE complexes during assembly, with depletion causing cellular blebbing and cytoskeletal dysfunction 1. Beyond its classical intracellular role, BRK1 functions as an extracellular signaling molecule released from dying myeloid cells following myocardial infarction 3. Extracellular BRK1 promotes cardiac angiogenesis via Rap-1 and MAPK1/3 signaling, leading to retinoblastoma protein hyperphosphorylation and E2F activation, thereby preserving cardiac function after ischemic injury 3. Genetically and proteomically, BRK1 dysregulation associates with multiple neurodegenerative diseases. BRK1 was identified as a genetically-driven dysregulated protein in Parkinson's disease pathogenesis 4 and shows association with Alzheimer's disease-related dementia risk through plasma proteome mediation 5. Additionally, BRK1 overexpression correlates with poor prognosis across multiple cancer types, including hepatocellular and cervical cancers, and associates with elevated tumor mutational burden and immune checkpoint expression, suggesting potential immunotherapy targeting 67. WAVE complex dysregulation broadly implicates BRK1 in developmental and neuropsychiatric disorders 8.