TRAPPC4 is a core component of the TRAPP complexes that functions as a guanine nucleotide exchange factor for Rab1 GTPase 1. Primary functions include mediating vesicular transport from the endoplasmic reticulum to the Golgi apparatus and regulating autophagy 1. Beyond canonical trafficking roles, TRAPPC4 regulates PD-L1 recycling by scaffolding interactions between PD-L1 and RAB11 in recycling endosomes, promoting tumor cell surface expression of this immunosuppressive ligand 2. TRAPPC4 also interacts with kalirin at recycling endosomes as part of a dual GEF complex coordinating Rab11 and Rac1 signaling 3. In colorectal cancer, TRAPPC4 interacts with ERK2 to promote its activation and nuclear translocation, enhancing cell proliferation 45. Clinically, biallelic loss-of-function variants in TRAPPC4 cause a neurodevelopmental disorder characterized by early-infantile onset, developmental regression, refractory seizures, progressive spasticity, microcephaly, and brain atrophy 678. The recurrent c.454+3A>G splice variant results in exon skipping, nonsense-mediated decay, and protein deficiency 6. TRAPPC4 represents a potential therapeutic target for enhancing anti-tumor immunity through PD-L1 modulation 2.