EXOC3L2 (exocyst complex component 3 like 2) functions as a component of the exocyst protein complex, mediating trafficking of post-Golgi vesicles to the plasma membrane 1. In endothelial cells, EXOC3L2 associates with exocyst proteins EXOC4 and EXOC7, and its upregulation occurs in response to VEGFA signaling, where it is essential for directional endothelial cell migration and angiogenesis 2. Complete loss of EXOC3L2 in mice results in embryonic lethality with hemorrhaging and disrupted cardiovascular and brain development 3. Biallelic EXOC3L2 mutations cause a multisystem syndrome affecting the brain, kidneys, and blood. Clinical manifestations include severe Dandy-Walker malformation with cerebellar vermis agenesis, white matter abnormalities, developmental delay, renal dysplasia, and bone marrow failure 1. EXOC3L2 variants have been identified as candidate genes in ciliopathy disorders 4 and in intrauterine lethal conditions 5. Additionally, the rs597668 polymorphism shows suggestive association with late-onset Alzheimer's disease risk in certain populations 678, though this association requires further validation independent of APOE ε4 status. EXOC3L2 represents a critical developmental gene whose dysfunction disrupts multiple organ systems.