TRAPPC6A is a subunit of the transport protein particle (TRAPP) complex, a highly conserved machinery essential for vesicular trafficking and membrane organization. 1 The protein functions in endoplasmic reticulum-to-Golgi transport and trans-Golgi network operations, where it interacts with other TRAPP components to regulate protein trafficking pathways. 2 TRAPPC6A can functionally replace its yeast ortholog, confirming evolutionary conservation of its trafficking role. 3 Molecularly, TRAPPC6A participates in TRAPP complex assembly and shows distinct binding preferences: it co-precipitates with both TRAPP II and TRAPP III complexes, contrasting with TRAPPC6B which preferentially associates with TRAPP II. 1 The protein is regulated post-translationally through proteasome-dependent mechanisms. 3 An N-terminal internal deletion isoform (TRAPPC6AΔ) derived from alternative splicing forms extracellular plaques in the brain and interacts with neurodegeneration-related proteins like WWOX, undergoing phosphorylation-dependent polymerization when WWOX is downregulated. 4 Clinically, mutations in TRAPPC6A associate with neurodevelopmental syndromes featuring intellectual disability, speech delay, and dysmorphic features including polydactyly. 3 TRAPPC6A upregulation occurs in white matter lesion development during cerebral hypoperfusion. 5 Additionally, TRAPPC6AΔ positively regulates influenza A virus replication by modulating M2 protein trafficking. 6