SYNRG (synergin gamma) is a membrane trafficking protein that plays essential roles in endocytosis and intracellular transport at the trans-Golgi network (TGN) 1. The protein functions as a component of clathrin-coated vesicles and forms a stable complex with aftiphilin and p200, which facilitates AP-1 adaptor complex function in protein trafficking 1. This complex is crucial for proper trafficking of transferrin from early to recycling endosomes and membrane trafficking of furin and cathepsin D between the TGN and endosomes 1. SYNRG has significant disease relevance, with mutations causing complicated hereditary spastic paraplegia, a neurodegenerative disorder affecting motor function 2. The gene has also been implicated in amyotrophic lateral sclerosis pathogenesis through regulatory networks involving MALAT1-mediated control 3. Additionally, SYNRG serves as a fusion partner in acute lymphoblastic leukemia, particularly in ZNF384-related rearrangements and novel SYNRG::TFEB fusions in renal cell carcinoma 45. Clinically, SYNRG variants should be evaluated in hereditary spastic paraplegia patients with unclear etiology, and rare variants may contribute to sarcopenia pathogenesis 26.