EXOC6B encodes a component of the exocyst complex, a multiprotein assembly critical for docking exocytic vesicles at the plasma membrane to enable targeted exocytosis 1. The protein functions in vesicle tethering and facilitates Golgi-to-plasma membrane transport, with additional roles in mitotic cytokinesis and membrane dynamics 1. Biallelic loss-of-function variants in EXOC6B cause spondyloepimetaphyseal dysplasia with joint laxity type 3 (SEMDJL3), characterized by multiple joint dislocations and skeletal abnormalities 1. The pathogenic mechanism involves impaired primary ciliogenesis due to abrogated exocytosis, reduced osteogenesis differentiation, and diminished extracellular matrix-related pathways 1. Affected individuals may exhibit additional complications including intellectual disability, hydrocephalus, and CNS anomalies 1, suggesting SEMDJL3 represents a ciliopathy with neurological involvement. Haploinsufficiency of EXOC6B also contributes to developmental phenotypes. Heterozygous deletions cause intellectual disability, speech delay, and craniofacial/skeletal abnormalities through disrupted Notch signaling 23. EXOC6B dysfunction appears linked to developmental processes requiring precise exocytotic control, with the exocyst complex playing an important role in intellectual development and morphogenesis 3.