TRAPPC1 (trafficking protein particle complex subunit 1) is a core component of the TRAPP tether complex essential for vesicular transport from the endoplasmic reticulum (ER) to the Golgi apparatus 1. The protein functions as part of a multisubunit complex regulating protein trafficking and acts as a guanine nucleotide exchange factor for Rab GTPases 2. Mechanistically, TRAPPC1 maintains ER homeostasis and protein transport fidelity. TRAPPC1 deficiency impairs ER-to-Golgi trafficking, triggering unfolded protein responses (UPR), enhanced oxidative stress, and ferroptosis through calcium-mitochondrial-dependent pathways 341. Diseased-relevant roles include: (1) Thymic epithelial cell (TEC) development—TRAPPC1 deficiency causes thymus atrophy with blocked TEC maturation, reduced Aire+ medullary TECs, and spontaneous autoimmunity 3; (2) Myeloid hematopoiesis—TRAPPC1 is essential for common myeloid progenitor maintenance and differentiation into monocytes/neutrophils 4; (3) T cell homeostasis—TRAPPC1 deficiency in naive T cells causes ferroptosis-mediated death and spontaneous autoinflammatory disease 1. Additionally, TRAPPC1 mutations cause rare neurodevelopmental disorders with myopathy 5. Clinically, TRAPPC1 dysfunction presents as immunodeficiency with autoimmunity and neurological/muscular complications, making it a critical therapeutic target for immune disorders.