Vacuolar protein sorting 45 homolog (VPS45)

Vacuolar protein sorting 45 homolog (VPS45) is a cytosolic protein belonging to the Sec1/Munc18 (SM) protein family, and plays a critical regulatory role in vesicle-mediated protein sorting, primarily within the endosomal system[1][3][7]. VPS45 functions as a key organizer of membrane trafficking between early endosomes and the trans-Golgi network by regulating the assembly of SNARE complexes and interacting with Rab5 effectors such as Rabenosyn-5 to facilitate endosomal fusion and receptor recycling[4][5]. It is required for neutrophil function, innate immunity, and proper hematopoiesis[1][2][5]. Mutations in VPS45 can disrupt endosomal-lysosomal transport, leading to severe congenital neutropenia, bone marrow fibrosis, myelofibrosis, platelet aggregation abnormalities, and (in some cases) neurological impairment[1][2][5]. Loss of VPS45 function can cause defective Rab5-to-Rab7 conversion, trapping cargo in early endosomes and impairing lysosomal delivery[5]. Knockout in mice is embryonically lethal, underscoring its essential role in development[5]. No specific drugs targeting VPS45 are currently identified, but the gene and its mutations serve as important biomarkers for inherited bone marrow failure syndromes, particularly for patient diagnosis and selection for bone marrow transplantation[2][5].

Other names

VPS45Vacuolar protein sorting-associated protein 45H-Vps45Leucocyte vacuolar protein sorting 45VPS45AVPS45BVacuolar protein sorting 45 homolog (S. cerevisiae)Vacuolar protein sorting 45A (yeast homolog)H1