CDC42EP5 (CDC42 effector protein 5), also known as BORG3, is a Cdc42 effector protein that functions as a key regulator of cytoskeletal organization and cell motility 1. The protein acts downstream of the small GTPase CDC42 to promote actin filament polymerization and organize septin cytoskeletal components 2. Mechanistically, CDC42EP5 associates with actin structures and modulates SEPT9 to enhance F-actin cross-linking and bundle formation, thereby increasing actomyosin contractility and enabling amoeboid cell migration 2. This activity is essential for pseudopodia formation in fibroblasts and regulation of cell shape. CDC42EP5 also inhibits MAPK8 independently of CDC42 binding, suggesting additional regulatory roles 1. In disease contexts, CDC42EP5 has emerged as significant in cancer biology. It is required for melanoma cell invasion and dissemination in collagen-rich matrices and in vivo metastasis 2. Genome-wide CRISPR-Cas9 screening identified CDC42EP5 as a gene whose knockout enhanced prostate cancer cell invasion and metastasis potential 3. CDC42EP5 was also identified as a fusion partner (SAMD1-CDC42EP5) in neuroblastic tumors and as an overexpressed gene in nodal marginal zone lymphoma 45. Additionally, CDC42EP5 was identified as a rescue gene in retinal degeneration models treated with neural progenitor cells 6.