TRAPPC12 is a core component of the TRAPPIII protein complex that functions in two distinct cellular processes: membrane trafficking and mitosis. In the secretory pathway, TRAPPC12 localizes to ER exit sites and the ER-Golgi intermediate compartment (ERGIC), where it positively modulates COPII vesicle coat assembly by binding to Sec13/Sec31A tetramers to facilitate ER-to-Golgi transport 1. TRAPPC12 is part of the TRAPPIII complex, which exhibits GEF activity specifically toward Rab1 and Rab43 GTPases, distinguishing it from TRAPPII 2. Beyond trafficking, TRAPPC12 (also called TRAMM) has a moonlighting mitotic function: it regulates chromosome 2 and kinetochore stability by controlling CENP-E recruitment to kinetochores in a phosphorylation-dependent manner 3. Biallelic TRAPPC12 mutations cause progressive early-onset encephalopathy with brain atrophy and spasticity (PEBAS), though phenotypic severity varies 45. Patient fibroblasts display fragmented Golgi morphology and delayed ER-to-Golgi transport 5. Additionally, TRAPPC12-AS1 (an antisense RNA) expression is associated with levodopa-induced dyskinesia susceptibility in Parkinson's disease patients 6. TRAPPC12 may also influence neurodegenerative disease pathology, with associations observed in Alzheimer's neuropathological trait analysis 7.