EXOC5 (exocyst complex component 5) is a central component of the highly conserved eight-protein exocyst complex that mediates vesicle tethering and docking at the plasma membrane 1. Beyond canonical exocytosis, EXOC5 plays critical roles in primary ciliogenesis across multiple tissues. In the kidney, EXOC5 is essential for renal ciliogenesis, cystogenesis, and tubulogenesis, with its ciliary targeting motif being functionally critical 2. Similarly, EXOC5 is required for photoreceptor ciliogenesis and retinal development; photoreceptor-specific knockout causes outer segment structural impairment and loss of visual responses 1. EXOC5 regulates extracellular vesicle (EV) production and protein content in a cilia-dependent manner, affecting EV cargo composition including ARF6 and EPS8L2 levels 3. In podocytes, EXOC5 is necessary for proper trafficking of slit diaphragm proteins (Neph1 and Nephrin); podocyte-specific knockout causes severe glomerular defects and proteinuria 4. EXOC5 expression is higher in floor plate progenitors than neural stem cells, consistent with its role in primary cilia signaling 5. During kidney fibrosis, EXOC5 plays a protective role by suppressing YAP activation; loss of EXOC5 exacerbates fibrosis progression 6. Additionally, rare variants in EXOC5 show suggestive association with late-onset Alzheimer's disease risk 7.